WorldWideScience

Sample records for model macromolecular systems

  1. Collagen macromolecular drug delivery systems

    International Nuclear Information System (INIS)

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t 1/2 and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and 14 C-inulin release rates were evaluated subcutaneously in rats

  2. Visual automated macromolecular model building.

    Science.gov (United States)

    Langer, Gerrit G; Hazledine, Saul; Wiegels, Tim; Carolan, Ciaran; Lamzin, Victor S

    2013-04-01

    Automated model-building software aims at the objective interpretation of crystallographic diffraction data by means of the construction or completion of macromolecular models. Automated methods have rapidly gained in popularity as they are easy to use and generate reproducible and consistent results. However, the process of model building has become increasingly hidden and the user is often left to decide on how to proceed further with little feedback on what has preceded the output of the built model. Here, ArpNavigator, a molecular viewer tightly integrated into the ARP/wARP automated model-building package, is presented that directly controls model building and displays the evolving output in real time in order to make the procedure transparent to the user.

  3. Structure studies of macromolecular systems

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich; Dohnálek, Jan; Skálová, Tereza; Dušková, Jarmila; Kolenko, Petr

    2006-01-01

    Roč. 13, č. 3 (2006), s. 136 ISSN 1211-5894. [Czech and Slovak Crystallographic Colloquium. 22.06.2006-24.06.2006, Grenoble] R&D Projects: GA AV ČR IAA4050811; GA MŠk 1K05008 Keywords : structure * X-ray diffraction * synchrotron Subject RIV: CD - Macromolecular Chemistry http://www. xray .cz/ms/default.htm

  4. Macromolecular Degradation Systems and Cardiovascular Aging.

    Science.gov (United States)

    Nakayama, Hiroyuki; Nishida, Kazuhiko; Otsu, Kinya

    2016-05-13

    Aging-related cardiovascular diseases are a rapidly increasing problem worldwide. Cardiac aging demonstrates progressive decline of diastolic dysfunction of ventricle and increase in ventricular and arterial stiffness accompanied by increased fibrosis stimulated by angiotensin II and proinflammatory cytokines. Reactive oxygen species and multiple signaling pathways on cellular senescence play major roles in the process. Aging is also associated with an alteration in steady state of macromolecular dynamics including a dysfunction of protein synthesis and degradation. Currently, impaired macromolecular degradation is considered to be closely related to enhanced inflammation and be involved in the process and mechanism of cardiac aging. Herein, we review the role and mechanisms of the degradation system of intracellular macromolecules in the process and pathophysiology of cardiovascular aging. © 2016 American Heart Association, Inc.

  5. Modeling the multi-scale mechanisms of macromolecular resource allocation

    DEFF Research Database (Denmark)

    Yang, Laurence; Yurkovich, James T; King, Zachary A

    2018-01-01

    As microbes face changing environments, they dynamically allocate macromolecular resources to produce a particular phenotypic state. Broad 'omics' data sets have revealed several interesting phenomena regarding how the proteome is allocated under differing conditions, but the functional consequen...... and detail how mathematical models have aided in our understanding of these processes. Ultimately, such modeling efforts have helped elucidate the principles of proteome allocation and hold promise for further discovery....

  6. A Compact X-Ray System for Macromolecular Crystallography. 5

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for macromolecular crystallography that combines a microfocus x-ray generator (40 gm FWHM spot size at a power level of 46.5Watts) and a 5.5 mm focal distance polycapillary optic. The Cu K(sub alpha) X-ray flux produced by this optimized system is 7.0 times above the X-ray flux previously reported. The X-ray flux from the microfocus system is also 3.2 times higher than that produced by the rotating anode generator equipped with a long focal distance graded multilayer monochromator (Green optic; CMF24-48-Cu6) and 30% less than that produced by the rotating anode generator with the newest design of graded multilayer monochromator (Blue optic; CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 Watts, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42,540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym) 5.0% for the data extending to 1.7A, and 4.8% for the complete set of data to 1.85A. The amplitudes of the reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  7. A Compact X-Ray System for Macromolecular Crystallography

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Gibson, Walter; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for a macromolecular crystallography that combines a microfocus x-ray generator (40 micrometer full width at half maximum spot size at a power level of 46.5 W) and a collimating polycapillary optic. The Cu Ka lpha x-ray flux produced by this optimized system through a 500,um diam orifice is 7.0 times greater than the x-ray flux previously reported by Gubarev et al. [M. Gubarev et al., J. Appl. Crystallogr. 33, 882 (2000)]. The x-ray flux from the microfocus system is also 2.6 times higher than that produced by a rotating anode generator equipped with a graded multilayer monochromator (green optic, Osmic Inc. CMF24-48-Cu6) and 40% less than that produced by a rotating anode generator with the newest design of graded multilayer monochromator (blue optic, Osmic, Inc. CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 W, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42 540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym)=5.0% for data extending to 1.70 A, and 4.8% for the complete set of data to 1.85 A. The amplitudes of the observed reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  8. The monitoring system for macromolecular crystallography beamlines at BSRF

    International Nuclear Information System (INIS)

    Guo Xian; Chang Guangcai; Gan Quan; Shi Hong; Liu Peng; Sun Gongxing

    2012-01-01

    The monitoring system for macromolecular crystallography beamlines at BSRF (Beijing Synchrotron Radiation Facility) based on LabVIEW is introduced. In order to guarantee a safe, stable, and reliable running for the beamline devices, the system monitors the state of vacuum, cooling-water, optical components, beam, Liquid nitrogen in the beamlines in real time, detects faults and gives the alarm timely. System underlying uses the driver developed for the field devices for data acquisition, Data of collection is uploaded to the data-sharing platform makes it accessible via a network share. The upper system divides modules according to the actual function, and establishes the main interface of the monitoring system of beamline. To Facilitate data storage, management and inquiry, the system use LabSQL toolkit to achieve the interconnection with MySQL database which data of collection is sent to. (authors)

  9. Data Management System at the Photon Factory Macromolecular Crystallography Beamline

    International Nuclear Information System (INIS)

    Yamada, Y; Matsugaki, N; Chavas, L M G; Hiraki, M; Igarashi, N; Wakatsuki, S

    2013-01-01

    Macromolecular crystallography is a very powerful tool to investigate three-dimensional structures of macromolecules at the atomic level, and is widely spread among structural biology researchers. Due to recent upgrades of the macromolecular crystallography beamlines at the Photon Factory, beamline throughput has improved, allowing more experiments to be conducted during a user's beam time. Although the number of beamlines has increased, so has the number of beam time applications. Consequently, both the experimental data from users' experiments and data derived from beamline operations have dramatically increased, causing difficulties in organizing these diverse and large amounts of data for the beamline operation staff and users. To overcome this problem, we have developed a data management system by introducing commercial middleware, which consists of a controller, database, and web servers. We have prepared several database projects using this system. Each project is dedicated to a certain aspect such as experimental results, beam time applications, beam time schedule, or beamline operation reports. Then we designed a scheme to link all the database projects.

  10. Macromolecular diffusion in crowded media beyond the hard-sphere model.

    Science.gov (United States)

    Blanco, Pablo M; Garcés, Josep Lluís; Madurga, Sergio; Mas, Francesc

    2018-04-25

    The effect of macromolecular crowding on diffusion beyond the hard-core sphere model is studied. A new coarse-grained model is presented, the Chain Entanglement Softened Potential (CESP) model, which takes into account the macromolecular flexibility and chain entanglement. The CESP model uses a shoulder-shaped interaction potential that is implemented in the Brownian Dynamics (BD) computations. The interaction potential contains only one parameter associated with the chain entanglement energetic cost (Ur). The hydrodynamic interactions are included in the BD computations via Tokuyama mean-field equations. The model is used to analyze the diffusion of a streptavidin protein among different sized dextran obstacles. For this system, Ur is obtained by fitting the streptavidin experimental long-time diffusion coefficient Dlongversus the macromolecular concentration for D50 (indicating their molecular weight in kg mol-1) dextran obstacles. The obtained Dlong values show better quantitative agreement with experiments than those obtained with hard-core spheres. Moreover, once parametrized, the CESP model is also able to quantitatively predict Dlong and the anomalous exponent (α) for streptavidin diffusion among D10, D400 and D700 dextran obstacles. Dlong, the short-time diffusion coefficient (Dshort) and α are obtained from the BD simulations by using a new empirical expression, able to describe the full temporal evolution of the diffusion coefficient.

  11. Macromolecular refinement by model morphing using non-atomic parameterizations.

    Science.gov (United States)

    Cowtan, Kevin; Agirre, Jon

    2018-02-01

    Refinement is a critical step in the determination of a model which explains the crystallographic observations and thus best accounts for the missing phase components. The scattering density is usually described in terms of atomic parameters; however, in macromolecular crystallography the resolution of the data is generally insufficient to determine the values of these parameters for individual atoms. Stereochemical and geometric restraints are used to provide additional information, but produce interrelationships between parameters which slow convergence, resulting in longer refinement times. An alternative approach is proposed in which parameters are not attached to atoms, but to regions of the electron-density map. These parameters can move the density or change the local temperature factor to better explain the structure factors. Varying the size of the region which determines the parameters at a particular position in the map allows the method to be applied at different resolutions without the use of restraints. Potential applications include initial refinement of molecular-replacement models with domain motions, and potentially the use of electron density from other sources such as electron cryo-microscopy (cryo-EM) as the refinement model.

  12. ISPyB: an information management system for synchrotron macromolecular crystallography.

    Science.gov (United States)

    Delagenière, Solange; Brenchereau, Patrice; Launer, Ludovic; Ashton, Alun W; Leal, Ricardo; Veyrier, Stéphanie; Gabadinho, José; Gordon, Elspeth J; Jones, Samuel D; Levik, Karl Erik; McSweeney, Seán M; Monaco, Stéphanie; Nanao, Max; Spruce, Darren; Svensson, Olof; Walsh, Martin A; Leonard, Gordon A

    2011-11-15

    Individual research groups now analyze thousands of samples per year at synchrotron macromolecular crystallography (MX) resources. The efficient management of experimental data is thus essential if the best possible experiments are to be performed and the best possible data used in downstream processes in structure determination pipelines. Information System for Protein crystallography Beamlines (ISPyB), a Laboratory Information Management System (LIMS) with an underlying data model allowing for the integration of analyses down-stream of the data collection experiment was developed to facilitate such data management. ISPyB is now a multisite, generic LIMS for synchrotron-based MX experiments. Its initial functionality has been enhanced to include improved sample tracking and reporting of experimental protocols, the direct ranking of the diffraction characteristics of individual samples and the archiving of raw data and results from ancillary experiments and post-experiment data processing protocols. This latter feature paves the way for ISPyB to play a central role in future macromolecular structure solution pipelines and validates the application of the approach used in ISPyB to other experimental techniques, such as biological solution Small Angle X-ray Scattering and spectroscopy, which have similar sample tracking and data handling requirements.

  13. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many ord...... problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data....... orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME...

  14. Modeling macromolecular degradation of corn starch in a twin screw extruder

    NARCIS (Netherlands)

    Einde, van den R.M.; Veen, van der M.E.; Bosman, H.; Goot, van der A.J.; Boom, R.M.

    2005-01-01

    Macromolecular degradation of starch in a twin screw extruder was modeled. A shear cell having well-defined flow conditions described earlier was used to measure peak viscosity of corn starch melts at various moisture contents and temperatures. Shear rate and elongation rate distributions in the

  15. Macromolecular query language (MMQL): prototype data model and implementation.

    Science.gov (United States)

    Shindyalov, I N; Chang, W; Pu, C; Bourne, P E

    1994-11-01

    Macromolecular query language (MMQL) is an extensible interpretive language in which to pose questions concerning the experimental or derived features of the 3-D structure of biological macromolecules. MMQL portends to be intuitive with a simple syntax, so that from a user's perspective complex queries are easily written. A number of basic queries and a more complex query--determination of structures containing a five-strand Greek key motif--are presented to illustrate the strengths and weaknesses of the language. The predominant features of MMQL are a filter and pattern grammar which are combined to express a wide range of interesting biological queries. Filters permit the selection of object attributes, for example, compound name and resolution, whereas the patterns currently implemented query primary sequence, close contacts, hydrogen bonding, secondary structure, conformation and amino acid properties (volume, polarity, isoelectric point, hydrophobicity and different forms of exposure). MMQL queries are processed by MMQLlib; a C++ class library, to which new query methods and pattern types are easily added. The prototype implementation described uses PDBlib, another C(++)-based class library from representing the features of biological macromolecules at the level of detail parsable from a PDB file. Since PDBlib can represent data stored in relational and object-oriented databases, as well as PDB files, once these data are loaded they too can be queried by MMQL. Performance metrics are given for queries of PDB files for which all derived data are calculated at run time and compared to a preliminary version of OOPDB, a prototype object-oriented database with a schema based on a persistent version of PDBlib which offers more efficient data access and the potential to maintain derived information. MMQLlib, PDBlib and associated software are available via anonymous ftp from cuhhca.hhmi.columbia.edu.

  16. The PDB_REDO server for macromolecular structure model optimization

    Directory of Open Access Journals (Sweden)

    Robbie P. Joosten

    2014-07-01

    Full Text Available The refinement and validation of a crystallographic structure model is the last step before the coordinates and the associated data are submitted to the Protein Data Bank (PDB. The success of the refinement procedure is typically assessed by validating the models against geometrical criteria and the diffraction data, and is an important step in ensuring the quality of the PDB public archive [Read et al. (2011, Structure, 19, 1395–1412]. The PDB_REDO procedure aims for `constructive validation', aspiring to consistent and optimal refinement parameterization and pro-active model rebuilding, not only correcting errors but striving for optimal interpretation of the electron density. A web server for PDB_REDO has been implemented, allowing thorough, consistent and fully automated optimization of the refinement procedure in REFMAC and partial model rebuilding. The goal of the web server is to help practicing crystallographers to improve their model prior to submission to the PDB. For this, additional steps were implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g. testing of resolution limits and k-fold cross-validation for small test sets, and as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS and ligand validation as implemented in YASARA. Innovative ways to present the refinement and validation results to the user are also described, which together with auto-generated Coot scripts can guide users to subsequent model inspection and improvement. It is demonstrated that using the server can lead to substantial improvement of structure models before they are submitted to the PDB.

  17. Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

    Directory of Open Access Journals (Sweden)

    Arghya Chakravorty

    2018-03-01

    Full Text Available Conventional modeling techniques to model macromolecular solvation and its effect on binding in the framework of Poisson-Boltzmann based implicit solvent models make use of a geometrically defined surface to depict the separation of macromolecular interior (low dielectric constant from the solvent phase (high dielectric constant. Though this simplification saves time and computational resources without significantly compromising the accuracy of free energy calculations, it bypasses some of the key physio-chemical properties of the solute-solvent interface, e.g., the altered flexibility of water molecules and that of side chains at the interface, which results in dielectric properties different from both bulk water and macromolecular interior, respectively. Here we present a Gaussian-based smooth dielectric model, an inhomogeneous dielectric distribution model that mimics the effect of macromolecular flexibility and captures the altered properties of surface bound water molecules. Thus, the model delivers a smooth transition of dielectric properties from the macromolecular interior to the solvent phase, eliminating any unphysical surface separating the two phases. Using various examples of macromolecular binding, we demonstrate its utility and illustrate the comparison with the conventional 2-dielectric model. We also showcase some additional abilities of this model, viz. to account for the effect of electrolytes in the solution and to render the distribution profile of water across a lipid membrane.

  18. In Vitro and In Vivo Evaluation of Microparticulate Drug Delivery Systems Composed of Macromolecular Prodrugs

    Directory of Open Access Journals (Sweden)

    Yoshiharu Machida

    2008-08-01

    Full Text Available Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.

  19. Preclinical imaging and translational animal models of cancer for accelerated clinical implementation of nanotechnologies and macromolecular agents.

    Science.gov (United States)

    De Souza, Raquel; Spence, Tara; Huang, Huang; Allen, Christine

    2015-12-10

    The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic models of cancer may enhance clinical translatability of preclinical studies focused on the development of nanotechnology-based drug delivery systems and macromolecular therapeutics, potentially accelerating their clinical implementation. It is recognized that the development and use of such models are not without challenge. Preclinical imaging tools offer a solution by allowing temporal and spatial characterization of metastatic lesions. This paper provides a review of imaging methods applicable for evaluation of novel therapeutics in clinically relevant models of advanced cancer. An overview of currently utilized models of oncology in small animals is followed by image-based development and characterization of visceral metastatic cancer models. Examples of imaging tools employed for metastatic lesion detection, evaluation of anti-tumor and anti-metastatic potential and biodistribution of novel therapies, as well as the co-development and/or use of imageable surrogates of response, are also discussed. While the focus is on development of macromolecular and nanotechnology-based therapeutics, examples with small molecules are included in some cases to illustrate concepts and approaches that can be applied in the assessment of nanotechnologies or macromolecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Macromolecular symmetric assembly prediction using swarm intelligence dynamic modeling.

    Science.gov (United States)

    Degiacomi, Matteo T; Dal Peraro, Matteo

    2013-07-02

    Proteins often assemble in multimeric complexes to perform a specific biologic function. However, trapping these high-order conformations is difficult experimentally. Therefore, predicting how proteins assemble using in silico techniques can be of great help. The size of the associated conformational space and the fact that proteins are intrinsically flexible structures make this optimization problem extremely challenging. Nonetheless, known experimental spatial restraints can guide the search process, contributing to model biologically relevant states. We present here a swarm intelligence optimization protocol able to predict the arrangement of protein symmetric assemblies by exploiting a limited amount of experimental restraints and steric interactions. Importantly, within this scheme the native flexibility of each protein subunit is taken into account as extracted from molecular dynamics (MD) simulations. We show that this is a key ingredient for the prediction of biologically functional assemblies when, upon oligomerization, subunits explore activated states undergoing significant conformational changes.

  1. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Shane Ó Conchúir

    Full Text Available The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  2. RosettaScripts: a scripting language interface to the Rosetta macromolecular modeling suite.

    Science.gov (United States)

    Fleishman, Sarel J; Leaver-Fay, Andrew; Corn, Jacob E; Strauch, Eva-Maria; Khare, Sagar D; Koga, Nobuyasu; Ashworth, Justin; Murphy, Paul; Richter, Florian; Lemmon, Gordon; Meiler, Jens; Baker, David

    2011-01-01

    Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins.

  3. Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Leimkuhler, B.; Hermans, J.; Skeel, R.D.

    1995-07-01

    A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

  4. Phenix - a comprehensive python-based system for macromolecular structure solution

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C [Los Alamos National Laboratory; Hung, Li - Wei [Los Alamos National Laboratory; Adams, Paul D [UC BERKELEY; Afonine, Pavel V [UC BERKELEY; Bunkoczi, Gabor [UNIV OF CAMBRIDGE; Chen, Vincent B [DUKE UNIV; Davis, Ian [DUKE UNIV; Echols, Nathaniel [LBNL; Headd, Jeffrey J [DUKE UNIV; Grosse Kunstleve, Ralf W [LBNL; Mccoy, Airlie J [UNIV OF CAMBRIDGE; Moriarty, Nigel W [LBNL; Oeffner, Robert [UNIV OF CAMBRIDGE; Read, Randy J [UNIV OF CAMBRIDGE; Richardson, David C [DUKE UNIV; Richardson, Jane S [DUKE UNIV; Zwarta, Peter H [LBNL

    2009-01-01

    Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages, and the repeated use of interactive three-dimensional graphics. Phenix has been developed to provide a comprehensive system for crystallographic structure solution with an emphasis on automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand, and finally the development of a framework that allows a tight integration between the algorithms.

  5. Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.; Adams, Paul D.; Moriarty, Nigel W.; Zwart, Peter; Read, Randy J.; Turk, Dusan; Hung, Li-Wei

    2007-01-01

    Heterogeneity in ensembles generated by independent model rebuilding principally reflects the limitations of the data and of the model-building process rather than the diversity of structures in the crystal. Automation of iterative model building, density modification and refinement in macromolecular crystallography has made it feasible to carry out this entire process multiple times. By using different random seeds in the process, a number of different models compatible with experimental data can be created. Sets of models were generated in this way using real data for ten protein structures from the Protein Data Bank and using synthetic data generated at various resolutions. Most of the heterogeneity among models produced in this way is in the side chains and loops on the protein surface. Possible interpretations of the variation among models created by repetitive rebuilding were investigated. Synthetic data were created in which a crystal structure was modelled as the average of a set of ‘perfect’ structures and the range of models obtained by rebuilding a single starting model was examined. The standard deviations of coordinates in models obtained by repetitive rebuilding at high resolution are small, while those obtained for the same synthetic crystal structure at low resolution are large, so that the diversity within a group of models cannot generally be a quantitative reflection of the actual structures in a crystal. Instead, the group of structures obtained by repetitive rebuilding reflects the precision of the models, and the standard deviation of coordinates of these structures is a lower bound estimate of the uncertainty in coordinates of the individual models

  6. Rapid automated superposition of shapes and macromolecular models using spherical harmonics.

    Science.gov (United States)

    Konarev, Petr V; Petoukhov, Maxim V; Svergun, Dmitri I

    2016-06-01

    A rapid algorithm to superimpose macromolecular models in Fourier space is proposed and implemented ( SUPALM ). The method uses a normalized integrated cross-term of the scattering amplitudes as a proximity measure between two three-dimensional objects. The reciprocal-space algorithm allows for direct matching of heterogeneous objects including high- and low-resolution models represented by atomic coordinates, beads or dummy residue chains as well as electron microscopy density maps and inhomogeneous multi-phase models ( e.g. of protein-nucleic acid complexes). Using spherical harmonics for the computation of the amplitudes, the method is up to an order of magnitude faster than the real-space algorithm implemented in SUPCOMB by Kozin & Svergun [ J. Appl. Cryst. (2001 ▸), 34 , 33-41]. The utility of the new method is demonstrated in a number of test cases and compared with the results of SUPCOMB . The spherical harmonics algorithm is best suited for low-resolution shape models, e.g . those provided by solution scattering experiments, but also facilitates a rapid cross-validation against structural models obtained by other methods.

  7. Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of Macromolecular Structures.

    Science.gov (United States)

    Viswanath, Shruthi; Chemmama, Ilan E; Cimermancic, Peter; Sali, Andrej

    2017-12-05

    Modeling of macromolecular structures involves structural sampling guided by a scoring function, resulting in an ensemble of good-scoring models. By necessity, the sampling is often stochastic, and must be exhaustive at a precision sufficient for accurate modeling and assessment of model uncertainty. Therefore, the very first step in analyzing the ensemble is an estimation of the highest precision at which the sampling is exhaustive. Here, we present an objective and automated method for this task. As a proxy for sampling exhaustiveness, we evaluate whether two independently and stochastically generated sets of models are sufficiently similar. The protocol includes testing 1) convergence of the model score, 2) whether model scores for the two samples were drawn from the same parent distribution, 3) whether each structural cluster includes models from each sample proportionally to its size, and 4) whether there is sufficient structural similarity between the two model samples in each cluster. The evaluation also provides the sampling precision, defined as the smallest clustering threshold that satisfies the third, most stringent test. We validate the protocol with the aid of enumerated good-scoring models for five illustrative cases of binary protein complexes. Passing the proposed four tests is necessary, but not sufficient for thorough sampling. The protocol is general in nature and can be applied to the stochastic sampling of any set of models, not just structural models. In addition, the tests can be used to stop stochastic sampling as soon as exhaustiveness at desired precision is reached, thereby improving sampling efficiency; they may also help in selecting a model representation that is sufficiently detailed to be informative, yet also sufficiently coarse for sampling to be exhaustive. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Macromolecular metabolism of a differentiated rat keratinocyte culture system following exposure to sulfur mustard

    International Nuclear Information System (INIS)

    Vaughan, F.L.; Zaman, S.; Scavarelli, R.; Bernstein, I.A.

    1988-01-01

    A method for producing a stratified, squamous epithelium in vitro by cultivating rat keratinocytes on nylon membranes has been developed in this laboratory. This epidermal-like culture is being used to obtain a better understanding of the mechanism of skin vesication after topical exposure to the sulfur mustard bis(beta-chloroethyl) sulfide (BCES) dissolved in a selected solvent. Radiolabeled macromolecular precursors (thymidine, uridine, and leucine) have been used to study the effect of BCES on the synthesis of DNA, RNA, and protein, respectively, after topical exposure to the mustard at concentrations of 0.01-500 nmol/cm2 dissolved in 70% dimethyl sulfoxide (DMSO). From these and other studies it has been determined that exposure to even the low concentration of 0.01 nmol BCES/cm2 for 30 min results in significant inhibition of [ 3 H]thymidine incorporation, although complete recovery occurs by 24 h. Significant inhibition of [ 3 H]uridine and [ 14 C]leucine incorporation is observed only after exposure to much higher concentrations of BCES (10-500 nmol/cm2). This suggests a very early lesion in macromolecular metabolism with DNA being the primary target

  9. Self-assembling supramolecular systems of different symmetry formed by wedged macromolecular dendrons

    Energy Technology Data Exchange (ETDEWEB)

    Shcherbina, M. A., E-mail: shcherbina@ispm.ru; Bakirov, A. V. [Russian Academy of Sciences, Institute of Synthetic Polymer Materials (Russian Federation); Yakunin, A. N. [Karpov Institute of Physical Chemistry (Russian Federation); Percec, V. [University of Pennsylvania (United States); Beginn, U. [Universitaet Osnabrueck, Institut fuer Chemie (Germany); Moeller, M. [Institute for Technical and Macromolecular Chemistry (Germany); Chvalun, S. N. [Russian Academy of Sciences, Institute of Synthetic Polymer Materials (Russian Federation)

    2012-03-15

    The main stages of the self-assembling of supramolecular ensembles have been revealed by studying different functional wedged macromolecules: polymethacrylates with tapered side chains based on gallic acid, their macromonomers, and salts of 2,3,4- and 3,4,5-tris(dodecyloxy)benzenesulphonic acid. The first stage is the formation of individual supramolecular aggregates (long cylinders or spherical micelles) due to the weak noncovalent interactions of mesogenic groups and the subsequent ordering in these aggregates, which is accompanied by a decrease in the free energy of the system. Supramolecular aggregates, in turn, form 2D or 3D lattices. The shape of supramolecular aggregates and its change with temperature are delicate functions of the mesogen chemical structure; this circumstance makes it possible to rationally design complex self-assembling systems with the ability to respond smartly to external stimuli. X-ray diffraction analysis allows one to study the structure of supramolecular systems with different degrees of order, determine the type of mesophases formed by these systems, and reveal the phase behavior of the material. Particular attention has been paid to the method for reconstruction of electron density distribution from the relative reflection intensity. The application of a suite of experimental methods, including wide- and small-angle X-ray diffraction, molecular modeling, differential scanning calorimetry, and polarization optical microscopy, allows one to establish the relationship between the shape of the structural unit (molecule or molecular aggregate), the nature of the interaction, and the phase behavior of the material.

  10. Self-assembling supramolecular systems of different symmetry formed by wedged macromolecular dendrons

    Science.gov (United States)

    Shcherbina, M. A.; Bakirov, A. V.; Yakunin, A. N.; Percec, V.; Beginn, U.; Möller, M.; Chvalun, S. N.

    2012-03-01

    The main stages of the self-assembling of supramolecular ensembles have been revealed by studying different functional wedged macromolecules: polymethacrylates with tapered side chains based on gallic acid, their macromonomers, and salts of 2,3,4- and 3,4,5-tris(dodecyloxy)benzenesulphonic acid. The first stage is the formation of individual supramolecular aggregates (long cylinders or spherical micelles) due to the weak noncovalent interactions of mesogenic groups and the subsequent ordering in these aggregates, which is accompanied by a decrease in the free energy of the system. Supramolecular aggregates, in turn, form 2D or 3D lattices. The shape of supramolecular aggregates and its change with temperature are delicate functions of the mesogen chemical structure; this circumstance makes it possible to rationally design complex self-assembling systems with the ability to respond smartly to external stimuli. X-ray diffraction analysis allows one to study the structure of supramolecular systems with different degrees of order, determine the type of mesophases formed by these systems, and reveal the phase behavior of the material. Particular attention has been paid to the method for reconstruction of electron density distribution from the relative reflection intensity. The application of a suite of experimental methods, including wide- and small-angle X-ray diffraction, molecular modeling, differential scanning calorimetry, and polarization optical microscopy, allows one to establish the relationship between the shape of the structural unit (molecule or molecular aggregate), the nature of the interaction, and the phase behavior of the material.

  11. Determination of macromolecular exchange and PO2 in the microcirculation: a simple system for in vivo fluorescence and phosphorescence videomicroscopy

    Directory of Open Access Journals (Sweden)

    Torres L.N.

    2001-01-01

    Full Text Available We have developed a system with two epi-illumination sources, a DC-regulated lamp for transillumination and mechanical switches for rapid shift of illumination and detection of defined areas (250-750 µm² by fluorescence and phosphorescence videomicroscopy. The system permits investigation of standard microvascular parameters, vascular permeability as well as intra- and extravascular PO2 by phosphorescence quenching of Pd-meso-tetra (4-carboxyphenyl porphine (PORPH. A Pechan prism was used to position a defined region over the photomultiplier and TV camera. In order to validate the system for in vivo use, in vitro tests were performed with probes at concentrations that can be found in microvascular studies. Extensive in vitro evaluations were performed by filling glass capillaries with solutions of various concentrations of FITC-dextran (diluted in blood and in saline mixed with different amounts of PORPH. Fluorescence intensity and phosphorescence decay were determined for each mixture. FITC-dextran solutions without PORPH and PORPH solutions without FITC-dextran were used as references. Phosphorescence decay curves were relatively unaffected by the presence of FITC-dextran at all concentrations tested (0.1 µg/ml to 5 mg/ml. Likewise, fluorescence determinations were performed in the presence of PORPH (0.05 to 0.5 mg/ml. The system was successfully used to study macromolecular extravasation and PO2 in the rat mesentery circulation under controlled conditions and during ischemia-reperfusion.

  12. JBluIce-EPICS: a fast and flexible open-source beamline control system for macromolecular crystallography

    Science.gov (United States)

    Stepanov, S.; Hilgart, M.; Makarov, O.; Pothineni, S. B.; Yoder, D.; Ogata, C.; Sanishvili, R.; Venugopalan, N.; Becker, M.; Clift, M.; Smith, J. L.; Fischetti, R. F.

    2013-03-01

    This paper overviews recent advances in the JBluIce-EPICS open-source control system designed at the macromolecular crystallography beamlines of the National Institute of General Medical Sciences and National Cancer Institute at the Advanced Photon Source (GM/CA@APS). We discuss some technical highlights of this system distinguishing it from the competition, such as reduction of software layers to only two, possibility to operate JBluIce in parallel with other beamline controls, plugin-enabled architecture where the plugins can be written in any programming language, and utilization of the whole power of the Java integrated development environment in the Graphical User Interface. Then, we demonstrate how these highlights help to make JBluIce fast, easily adaptable to new beamline developments, and intuitive for users. In particular, we discuss several recent additions to the system including a bridge between crystal rastering and data collection, automatic detection of raster polygons from optical crystal centering, background data processing, and a pathway to a fully automated pipeline from crystal screening to solving crystal structure.

  13. Normal mode analysis of macromolecular systems with the mobile block Hessian method

    International Nuclear Information System (INIS)

    Ghysels, An; Van Speybroeck, Veronique; Van Neck, Dimitri; Waroquier, Michel; Brooks, Bernard R.

    2015-01-01

    Until recently, normal mode analysis (NMA) was limited to small proteins, not only because the required energy minimization is a computationally exhausting task, but also because NMA requires the expensive diagonalization of a 3N a ×3N a matrix with N a the number of atoms. A series of simplified models has been proposed, in particular the Rotation-Translation Blocks (RTB) method by Tama et al. for the simulation of proteins. It makes use of the concept that a peptide chain or protein can be seen as a subsequent set of rigid components, i.e. the peptide units. A peptide chain is thus divided into rigid blocks with six degrees of freedom each. Recently we developed the Mobile Block Hessian (MBH) method, which in a sense has similar features as the RTB method. The main difference is that MBH was developed to deal with partially optimized systems. The position/orientation of each block is optimized while the internal geometry is kept fixed at a plausible - but not necessarily optimized - geometry. This reduces the computational cost of the energy minimization. Applying the standard NMA on a partially optimized structure however results in spurious imaginary frequencies and unwanted coordinate dependence. The MBH avoids these unphysical effects by taking into account energy gradient corrections. Moreover the number of variables is reduced, which facilitates the diagonalization of the Hessian. In the original implementation of MBH, atoms could only be part of one rigid block. The MBH is now extended to the case where atoms can be part of two or more blocks. Two basic linkages can be realized: (1) blocks connected by one link atom, or (2) by two link atoms, where the latter is referred to as the hinge type connection. In this work we present the MBH concept and illustrate its performance with the crambin protein as an example

  14. A Microfluidics-HPLC/Differential Mobility Spectrometer Macromolecular Detection System for Human and Robotic Missions

    Science.gov (United States)

    Coy, S. L.; Killeen, K.; Han, J.; Eiceman, G. A.; Kanik, I.; Kidd, R. D.

    2011-01-01

    Our goal is to develop a unique, miniaturized, solute analyzer based on microfluidics technology. The analyzer consists of an integrated microfluidics High Performance Liquid Chromatographic chip / Differential Mobility Spectrometer (?HPLCchip/ DMS) detection system

  15. Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions

    International Nuclear Information System (INIS)

    Brown, Alan; Long, Fei; Nicholls, Robert A.; Toots, Jaan; Emsley, Paul; Murshudov, Garib

    2015-01-01

    A description is given of new tools to facilitate model building and refinement into electron cryo-microscopy reconstructions. The recent rapid development of single-particle electron cryo-microscopy (cryo-EM) now allows structures to be solved by this method at resolutions close to 3 Å. Here, a number of tools to facilitate the interpretation of EM reconstructions with stereochemically reasonable all-atom models are described. The BALBES database has been repurposed as a tool for identifying protein folds from density maps. Modifications to Coot, including new Jiggle Fit and morphing tools and improved handling of nucleic acids, enhance its functionality for interpreting EM maps. REFMAC has been modified for optimal fitting of atomic models into EM maps. As external structural information can enhance the reliability of the derived atomic models, stabilize refinement and reduce overfitting, ProSMART has been extended to generate interatomic distance restraints from nucleic acid reference structures, and a new tool, LIBG, has been developed to generate nucleic acid base-pair and parallel-plane restraints. Furthermore, restraint generation has been integrated with visualization and editing in Coot, and these restraints have been applied to both real-space refinement in Coot and reciprocal-space refinement in REFMAC

  16. Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Alan; Long, Fei; Nicholls, Robert A.; Toots, Jaan; Emsley, Paul; Murshudov, Garib, E-mail: garib@mrc-lmb.cam.ac.uk [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH (United Kingdom)

    2015-01-01

    A description is given of new tools to facilitate model building and refinement into electron cryo-microscopy reconstructions. The recent rapid development of single-particle electron cryo-microscopy (cryo-EM) now allows structures to be solved by this method at resolutions close to 3 Å. Here, a number of tools to facilitate the interpretation of EM reconstructions with stereochemically reasonable all-atom models are described. The BALBES database has been repurposed as a tool for identifying protein folds from density maps. Modifications to Coot, including new Jiggle Fit and morphing tools and improved handling of nucleic acids, enhance its functionality for interpreting EM maps. REFMAC has been modified for optimal fitting of atomic models into EM maps. As external structural information can enhance the reliability of the derived atomic models, stabilize refinement and reduce overfitting, ProSMART has been extended to generate interatomic distance restraints from nucleic acid reference structures, and a new tool, LIBG, has been developed to generate nucleic acid base-pair and parallel-plane restraints. Furthermore, restraint generation has been integrated with visualization and editing in Coot, and these restraints have been applied to both real-space refinement in Coot and reciprocal-space refinement in REFMAC.

  17. Investigation of biological macromolecular systems with a pulsed neutron source: a review

    International Nuclear Information System (INIS)

    Cser, L.

    1976-01-01

    The investigation of biological macromolecules and crystalline structures by SAS and diffraction of neutrons with the TOF method indicates that the main difficulties of the TOF method (the wavelength dependence of the incident beam, resolution power, and detector efficiency; the need for their determination and up-to-date values) are compensated for by its advantages. Both methods allow a high data accumulation rate and optimal employment of the incident neutron spectrum. The latter has been achieved by utilizing a dominant part of the Maxwellian spectrum and by a more uniform distribution of statistical accuracy over the most informative measuring range. Another advantage is the high degree of monochromatization of the incident neutron beam by the TOF method. The rigid requirements concerning the data accumulation rate and the capacity of the on-line system computer memory are technical problems but not basic ones

  18. Investigation of biological macromolecular systems with a pulsed neutron source--a review.

    Science.gov (United States)

    Cser, L

    1976-05-01

    The conclusion that can be drawn on the basis of the above considerations is that investigation of biological macromolecules and crystalline structures by SAS and diffraction of neutrons with the TOF method is feasible. The main difficulties of the TOF method (the wavelength dependence of the incident beam, resolution power, and detector efficiency; the need for their determination and up-to-date values) are compensated for by its advantages. Both methods allow a high data accumulation rate and optimal employment of the incident neutron spectrum. The latter has been achieved by utilizing a dominant part of the Maxwellian spectrum and by a more uniform distribution of statistical accuracy over the most informative measuring range. Another advantage is the high degree of monochronatization of the incident neutron beam by the TOF method. The rigid requirements concerning the data accumulation rate and the capacity of the on-line system computer memory are technical problems but not basic ones.

  19. Macromolecular prodrugs of ribavirin

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Kryger, Mille

    2015-01-01

    -infection increasingly challenging. Herein we report the first design of macromolecular prodrugs (MP) with concurrent success in fighting HIV and alleviating hepatitis (liver inflammation). To achieve this, polymer compositions were systematically screened in a broad range of molar mass and content of ribavirin...

  20. Macromolecular Crystallization in Microgravity

    Science.gov (United States)

    Snell, Edward H.; Helliwell, John R.

    2004-01-01

    The key concepts that attracted crystal growers, macromolecular or solid state, to microgravity research is that density difference fluid flows and sedimentation of the growing crystals are greatly reduced. Thus, defects and flaws in the crystals can be reduced, even eliminated, and crystal volume can be increased. Macromolecular crystallography differs from the field of crystalline semiconductors. For the latter, crystals are harnessed for their electrical behaviors. A crystal of a biological macromolecule is used instead for diffraction experiments (X-ray or neutron) to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal of a biological macromolecule then the more molecular structure detail that can be extracted. This structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences with major potential in understanding disease pathologies. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry, and mathematics meet to enable insight to the basic fundamentals of life. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment, and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyze the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural

  1. Structure analysis of molecular systems in the Institute of Macromolecular Chemistry of the Czech Academy of Sciences

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich

    2010-01-01

    Roč. 17, 2a (2010), k32-k34 ISSN 1211-5894. [Struktura 2010. Soláň, 14.06.2010-17.06.2010] R&D Projects: GA AV ČR IAA500500701; GA ČR GA305/07/1073 Institutional research plan: CEZ:AV0Z40500505 Keywords : Academy of Sciences of the Czech Republic * X-ray structure analysis * crystallography Subject RIV: CD - Macromolecular Chemistry http:// xray .cz/ms/bul2010-2a/hasek.pdf

  2. Data Mining of Macromolecular Structures.

    Science.gov (United States)

    van Beusekom, Bart; Perrakis, Anastassis; Joosten, Robbie P

    2016-01-01

    The use of macromolecular structures is widespread for a variety of applications, from teaching protein structure principles all the way to ligand optimization in drug development. Applying data mining techniques on these experimentally determined structures requires a highly uniform, standardized structural data source. The Protein Data Bank (PDB) has evolved over the years toward becoming the standard resource for macromolecular structures. However, the process selecting the data most suitable for specific applications is still very much based on personal preferences and understanding of the experimental techniques used to obtain these models. In this chapter, we will first explain the challenges with data standardization, annotation, and uniformity in the PDB entries determined by X-ray crystallography. We then discuss the specific effect that crystallographic data quality and model optimization methods have on structural models and how validation tools can be used to make informed choices. We also discuss specific advantages of using the PDB_REDO databank as a resource for structural data. Finally, we will provide guidelines on how to select the most suitable protein structure models for detailed analysis and how to select a set of structure models suitable for data mining.

  3. Macromolecular crystallization in microgravity

    International Nuclear Information System (INIS)

    Snell, Edward H; Helliwell, John R

    2005-01-01

    Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment. In the case of macromolecular crystallography a crystal of a biological macromolecule is used for diffraction experiments (x-ray or neutron) so as to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal then the greater the molecular structure detail that can be extracted. It is this structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences, with major potential in understanding disease pathologies. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyse the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry and mathematics meet to enable insight to the fundamentals of life. As the reader will see, there is a great deal of physics involved when the microgravity environment is applied to crystallization, some of it known, and undoubtedly much yet to

  4. Effect of macromolecular crowding on the rate of diffusion-limited ...

    Indian Academy of Sciences (India)

    The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some ...

  5. Microgravity and Macromolecular Crystallography

    Science.gov (United States)

    Kundrot, Craig E.; Judge, Russell A.; Pusey, Marc L.; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Macromolecular crystal growth has been seen as an ideal experiment to make use of the reduced acceleration environment provided by an orbiting spacecraft. The experiments are small, simply operated and have a high potential scientific and economic impact. In this review we examine the theoretical reasons why microgravity should be a beneficial environment for crystal growth and survey the history of experiments on the Space Shuttle Orbiter, on unmanned spacecraft, and on the Mir space station. Finally we outline the direction for optimizing the future use of orbiting platforms.

  6. Complex macromolecular chimeras.

    Science.gov (United States)

    Karatzas, Anastasis; Iatrou, Hermis; Hadjichristidis, Nikos; Inoue, Kyouichi; Sugiyama, Kenji; Hirao, Akira

    2008-07-01

    By combining two living polymerizations, anionic and ring opening (ROP), the following novel multiblock multicomponent linear and miktoarm star (micro-star) polymer/polypeptide hybrids (macromolecular chimeras) were synthesized: Linear, PBLL-b-PBLG-b-PS-b-PBLG-b-PBLL; 3micro-stars, (PS)2(PBLG or PBLL), (PS)(PI)(PBLG or PBLL); 4micro-stars, (PS)2[P(alpha-MeS)](PBLG or PBLL), (PS)2(PBLG or PBLL)2 [PS, polystyrene; PI, polyisoprene; P(alpha-MeS), poly(alpha-methylstyrene); PBLG, poly(gamma-benzyl-L-glutamate); and PBLL, poly(-tert-butyloxycarbonyl-L-lysine)]. The procedure involves (a) the synthesis of end- or in-chain amino-functionalized polymers, by anionic polymerization high vacuum techniques and appropriate linking chemistry and (b) the use of the amino groups for the ROP of alpha-amino acid carboxyanhydrides (NCAs). Molecular characterization revealed the high molecular weight and compositional homogeneity of the macromolecular chimeras prepared. The success of the synthesis was based mainly on the high vacuum techniques used for the ROP of NCAs, ensuring the avoidance of unwanted polymerization mechanisms and termination reactions.

  7. Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

  8. Continuous mutual improvement of macromolecular structure models in the PDB and of X-ray crystallographic software: the dual role of deposited experimental data

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov [Los Alamos National Laboratory, Mail Stop M888, Los Alamos, NM 87507 (United States); Bricogne, Gerard, E-mail: terwilliger@lanl.gov [Global Phasing Ltd, Sheraton House, Castle Park, Cambridge CB3 0AX (United Kingdom); Los Alamos National Laboratory, Mail Stop M888, Los Alamos, NM 87507 (United States)

    2014-10-01

    Macromolecular structures deposited in the PDB can and should be continually reinterpreted and improved on the basis of their accompanying experimental X-ray data, exploiting the steady progress in methods and software that the deposition of such data into the PDB on a massive scale has made possible. Accurate crystal structures of macromolecules are of high importance in the biological and biomedical fields. Models of crystal structures in the Protein Data Bank (PDB) are in general of very high quality as deposited. However, methods for obtaining the best model of a macromolecular structure from a given set of experimental X-ray data continue to progress at a rapid pace, making it possible to improve most PDB entries after their deposition by re-analyzing the original deposited data with more recent software. This possibility represents a very significant departure from the situation that prevailed when the PDB was created, when it was envisioned as a cumulative repository of static contents. A radical paradigm shift for the PDB is therefore proposed, away from the static archive model towards a much more dynamic body of continuously improving results in symbiosis with continuously improving methods and software. These simultaneous improvements in methods and final results are made possible by the current deposition of processed crystallographic data (structure-factor amplitudes) and will be supported further by the deposition of raw data (diffraction images). It is argued that it is both desirable and feasible to carry out small-scale and large-scale efforts to make this paradigm shift a reality. Small-scale efforts would focus on optimizing structures that are of interest to specific investigators. Large-scale efforts would undertake a systematic re-optimization of all of the structures in the PDB, or alternatively the redetermination of groups of structures that are either related to or focused on specific questions. All of the resulting structures should be

  9. Functional Sub-states by High-pressure Macromolecular Crystallography.

    Science.gov (United States)

    Dhaussy, Anne-Claire; Girard, Eric

    2015-01-01

    At the molecular level, high-pressure perturbation is of particular interest for biological studies as it allows trapping conformational substates. Moreover, within the context of high-pressure adaptation of deep-sea organisms, it allows to decipher the molecular determinants of piezophily. To provide an accurate description of structural changes produced by pressure in a macromolecular system, developments have been made to adapt macromolecular crystallography to high-pressure studies. The present chapter is an overview of results obtained so far using high-pressure macromolecular techniques, from nucleic acids to virus capsid through monomeric as well as multimeric proteins.

  10. Macromolecular synthesis in algal cells

    International Nuclear Information System (INIS)

    Ishida, M.R.; Kikuchi, Tadatoshi

    1980-01-01

    The present paper is a review of our experimental results obtained previously on the macromolecular biosyntheses in the cells of blue-green alga Anacystis nidulans as a representative species of prokaryote, and also in those of three species of eukaryotic algae, i.e. Euglena gracilis strain Z, Chlamydomonas reinhardi, and Cyanidium caldarium. In these algal cells, the combined methods consisting of pulse-labelling using 32 P, 3 H- and 14 C-labelled precursors for macromolecules, of their chasing and of the use of inhibitors which block specifically the syntheses of macromolecules such as proteins, RNA and DNA in living cells were very effectively applied for the analyses of the regulatory mechanism in biosyntheses of macromolecules and of the mode of their assembly into the cell structure, especially organelle constituents. Rased on the results obtained thus, the following conclusions are reached: (1) the metabolic pool for syntheses of macromolecules in the cells of prokaryotic blue-green alga is limited to the small extent and such activities couple largely with the photosynthetic mechanism; (2) 70 S ribosomes in the blue-green algal cells are assembled on the surface of thylakoid membranes widely distributed in their cytoplasm; and (3) the cells of eukaryotic unicellular algae used here have biochemical characters specific for already differentiated enzyme system involving in transcription and translation machineries as the same as in higher organisms, but the control mechanism concerning with such macromolecule syntheses are different among each species. (author)

  11. The Phenix software for automated determination of macromolecular structures.

    Science.gov (United States)

    Adams, Paul D; Afonine, Pavel V; Bunkóczi, Gábor; Chen, Vincent B; Echols, Nathaniel; Headd, Jeffrey J; Hung, Li-Wei; Jain, Swati; Kapral, Gary J; Grosse Kunstleve, Ralf W; McCoy, Airlie J; Moriarty, Nigel W; Oeffner, Robert D; Read, Randy J; Richardson, David C; Richardson, Jane S; Terwilliger, Thomas C; Zwart, Peter H

    2011-09-01

    X-ray crystallography is a critical tool in the study of biological systems. It is able to provide information that has been a prerequisite to understanding the fundamentals of life. It is also a method that is central to the development of new therapeutics for human disease. Significant time and effort are required to determine and optimize many macromolecular structures because of the need for manual interpretation of complex numerical data, often using many different software packages, and the repeated use of interactive three-dimensional graphics. The Phenix software package has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on automation. This has required the development of new algorithms that minimize or eliminate subjective input in favor of built-in expert-systems knowledge, the automation of procedures that are traditionally performed by hand, and the development of a computational framework that allows a tight integration between the algorithms. The application of automated methods is particularly appropriate in the field of structural proteomics, where high throughput is desired. Features in Phenix for the automation of experimental phasing with subsequent model building, molecular replacement, structure refinement and validation are described and examples given of running Phenix from both the command line and graphical user interface. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Highlighting cancer cells with macromolecular probes

    Science.gov (United States)

    Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Brown, Adrienne S.; Wilson, James N.; Raymo, Françisco M.

    2017-02-01

    Conventional fluorophore-ligand constructs for the detection of cancer cells generally produce relatively weak signals with modest contrast. The inherently low brightness accessible per biding event with the pairing of a single organic fluorophore to a single ligand as well as the contribution of unbound probes to background fluorescence are mainly responsible for these limitations. Our laboratories identified a viable structural design to improve both brightness and contrast. It is based on the integration of activatable fluorophores and targeting ligands within the same macromolecular construct. The chromophoric components are engineered to emit bright fluorescence exclusively in acidic environments. The targeting agents are designed to bind complementary receptors overexpressed on the surface of cancer cells and allow internalization of the macromolecules into acidic organelles. As a result of these properties, our macromolecular probes switch their intense emission on exclusively in the intracellular space of target cells with minimal background fluorescence from the extracellular matrix. In fact, these operating principles translate into a 170-fold enhancement in brightness, relative to equivalent but isolated chromophoric components, and a 3-fold increase in contrast, relative to model but non-activatable fluorophores. Thus, our macromolecular probes might ultimately evolve into valuable analytical tools to highlight cancer cells with optimal signal-to-noise ratios in a diversity of biomedical applications.

  13. Recent advances in macromolecular prodrugs

    DEFF Research Database (Denmark)

    Riber, Camilla Frich; Zelikin, Alexander N.

    2017-01-01

    Macromolecular prodrugs (MP) are high molar mass conjugates, typically carrying several copies of a drug or a drug combination, designed to optimize delivery of the drug, that is — its pharmacokinetics. From its advent several decades ago, design of MP has undergone significant development...

  14. Macromolecular systems for vaccine delivery

    Czech Academy of Sciences Publication Activity Database

    Mužíková, Gabriela; Laga, Richard

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S203-S216 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : vaccine delivery * cellular and humoral immunity * polymer immunostimulants Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S203.pdf

  15. Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system

    Czech Academy of Sciences Publication Activity Database

    Filippov, Sergey K.; Chytil, Petr; Konarev, P. V.; Dyakonova, M.; Papadakis, C. M.; Zhigunov, Alexander; Pleštil, Josef; Štěpánek, Petr; Etrych, Tomáš; Ulbrich, Karel; Svergun, D. I.

    2012-01-01

    Roč. 13, č. 8 (2012), s. 2594-2604 ISSN 1525-7797 R&D Projects: GA MŠk ME09059; GA AV ČR IAAX00500803; GA ČR GAP108/12/0640 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : HPMA * cholesterol * SAXS Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.371, year: 2012

  16. Development of macromolecular prodrug for rheumatoid arthritis.

    Science.gov (United States)

    Yuan, Fang; Quan, Ling-dong; Cui, Liao; Goldring, Steven R; Wang, Dong

    2012-09-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that is considered to be one of the major public health problems worldwide. The development of therapies that target tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and co-stimulatory pathways that regulate the immune system have revolutionized the care of patients with RA. Despite these advances, many patients continue to experience symptomatic and functional impairment. To address this issue, more recent therapies that have been developed are designed to target intracellular signaling pathways involved in immunoregulation. Though this approach has been encouraging, there have been major challenges with respect to off-target organ side effects and systemic toxicities related to the widespread distribution of these signaling pathways in multiple cell types and tissues. These limitations have led to an increasing interest in the development of strategies for the macromolecularization of anti-rheumatic drugs, which could target them to the inflamed joints. This approach enhances the efficacy of the therapeutic agent with respect to synovial inflammation, while markedly reducing non-target organ adverse side effects. In this manuscript, we provide a comprehensive overview of the rational design and optimization of macromolecular prodrugs for treatment of RA. The superior and the sustained efficacy of the prodrug may be partially attributed to their Extravasation through Leaky Vasculature and subsequent Inflammatory cell-mediated Sequestration (ELVIS) in the arthritic joints. This biologic process provides a plausible mechanism, by which macromolecular prodrugs preferentially target arthritic joints and illustrates the potential benefits of applying this therapeutic strategy to the treatment of other inflammatory diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Transition dipole coupling modeling of optical activity enhancements in macromolecular protein systems

    Czech Academy of Sciences Publication Activity Database

    Průša, Jiří; Bouř, Petr

    2018-01-01

    Roč. 30, č. 1 (2018), s. 55-64 ISSN 0899-0042 R&D Projects: GA ČR GA15-09072S; GA MŠk(CZ) LTC17012 Institutional support: RVO:61388963 Keywords : optical activity * vibrational circular dichroism * protein fibrils Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 1.956, year: 2016

  18. Experimental procedure for the characterization of radiation damage in macromolecular crystals

    International Nuclear Information System (INIS)

    Leal, Ricardo M. F.; Bourenkov, Gleb P.; Svensson, Olof; Spruce, Darren; Guijarro, Matias; Popov, Alexander N.

    2011-01-01

    A novel automatic procedure to determine the sensitivity of macromolecular crystals to radiation damage is presented. The information extracted from this procedure can be directly used for optimal planning of data collection or/and beamline calibration. A reliable and reproducible method to automatically characterize the radiation sensitivity of macromolecular crystals at the ESRF beamlines has been developed. This new approach uses the slope of the linear dependence of the overall isotropic B-factor with absorbed dose as the damage metric. The method has been implemented through an automated procedure using the EDNA on-line data analysis framework and the MxCuBE data collection control interface. The outcome of the procedure can be directly used to design an optimal data collection strategy. The results of tests carried out on a number of model and real-life crystal systems are presented

  19. Reexamining the molecular/macromolecular model of coal from comparative in situ variable-temperature {sup 1}H NMR studies of Argonne Premium coal 601 and its pyridine extraction residue

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, J.; Maciel, G.E. [Colorado State University, Fort Collins, CO (United States). Dept. of Chemistry

    2002-06-01

    We have carried out the first systematic in situ variable-temperature {sup 1}H NMR study, using the CRAMPS (combined rotation and multiple pulse spectroscopy) technique of the residue from pyridine extraction of Argonne premium coal 601. The change of molecular mobility in the residue under various thermal treatments and pyridine swelling conditions were monitored quantitatively through a proton dipolar-dephasing experiment based on CRAMPS detection. Correlations among molecular structure, molecular mobility and solvent-extraction components were established through comparative variable-temperature {sup 1}H CRAMPS studies on the C{sub 5}D{sub 5}N-saturated original coal and its extraction residue. A critical review of the molecular/macromolecular (M/M) structural model of coal has been made on the basis of the new results, showing that the relationships between the M/M model and molecular dynamics is much more complicated than previously thought. Both the molecular phase and the macromolecular phase can show molecular dynamics behavior ranging from a lack of substantial motion to extremely mobile behaviour with correlation times as short as 30 ns. Without systematic variable temperature studies, correlation between molecular mobility and the M/M model cannot be established correctly by NMR. 28 refs., 7 figs., 6 tabs.

  20. Macromolecular crystallographic estructure refinement

    Directory of Open Access Journals (Sweden)

    Afonine, Pavel V.

    2015-04-01

    Full Text Available Model refinement is a key step in crystallographic structure determination that ensures final atomic structure of macromolecule represents measured diffraction data as good as possible. Several decades have been put into developing methods and computational tools to streamline this step. In this manuscript we provide a brief overview of major milestones of crystallographic computing and methods development pertinent to structure refinement.El refinamiento es un paso clave en el proceso de determinación de una estructura cristalográfica al garantizar que la estructura atómica de la macromolécula final represente de la mejor manera posible los datos de difracción. Han hecho falta varias décadas para poder desarrollar nuevos métodos y herramientas computacionales dirigidas a dinamizar esta etapa. En este artículo ofrecemos un breve resumen de los principales hitos en la computación cristalográfica y de los nuevos métodos relevantes para el refinamiento de estructuras.

  1. Neutron Laue macromolecular crystallography.

    Science.gov (United States)

    Meilleur, Flora; Myles, Dean A A; Blakeley, Matthew P

    2006-09-01

    Recent progress in neutron protein crystallography such as the use of the Laue technique and improved neutron optics and detector technologies have dramatically improved the speed and precision with which neutron protein structures can now be determined. These studies are providing unique and complementary insights on hydrogen and hydration in protein crystal structures that are not available from X-ray structures alone. Parallel improvements in modern molecular biology now allow fully (per)deuterated protein samples to be produced for neutron scattering that essentially eradicate the large-and ultimately limiting-hydrogen incoherent scattering background that has hampered such studies in the past. High quality neutron data can now be collected to near atomic resolution (approximately 2.0 A) for proteins of up to approximately 50 kDa molecular weight using crystals of volume approximately 0.1 mm3 on the Laue diffractometer at ILL. The ability to flash-cool and collect high resolution neutron data from protein crystals at cryogenic temperature (15 K) has opened the way for kinetic crystallography on freeze trapped systems. Current instrument developments now promise to reduce crystal volume requirements by a further order of magnitude, making neutron protein crystallography a more accessible and routine technique.

  2. Synthetic Macromolecular Antibiotic Platform for Inhalable Therapy against Aerosolized Intracellular Alveolar Infections.

    Science.gov (United States)

    Das, Debobrato; Chen, Jasmin; Srinivasan, Selvi; Kelly, Abby M; Lee, Brian; Son, Hye-Nam; Radella, Frank; West, T Eoin; Ratner, Daniel M; Convertine, Anthony J; Skerrett, Shawn J; Stayton, Patrick S

    2017-06-05

    Lung-based intracellular bacterial infections remain one of the most challenging infectious disease settings. For example, the current standard for treating Franciscella tularensis pneumonia (tularemia) relies on administration of oral or intravenous antibiotics that poorly achieve and sustain pulmonary drug bioavailability. Inhalable antibiotic formulations are approved and in clinical development for upper respiratory infections, but sustained drug dosing from inhaled antibiotics against alveolar intracellular infections remains a current unmet need. To provide an extended therapy against alveolar intracellular infections, we have developed a macromolecular therapeutic platform that provides sustained local delivery of ciprofloxacin with controlled dosing profiles. Synthesized using RAFT polymerization, these macromolecular prodrugs characteristically have high drug loading (16-17 wt % drug), tunable hydrolysis kinetics mediated by drug linkage chemistry (slow-releasing alkyllic vs fast-releasing phenolic esters), and, in general, represent new fully synthetic nanotherapeutics with streamlined manufacturing profiles. In aerosolized and completely lethal F.t. novicida mouse challenge models, the fast-releasing ciprofloxacin macromolecular prodrug provided high cure efficiencies (75% survival rate under therapeutic treatment), and the importance of release kinetics was demonstrated by the inactivity of the similar but slow-releasing prodrug system. Pharmacokinetics and biodistribution studies further demonstrated that the efficacious fast-releasing prodrug retained drug dosing in the lung above the MIC over a 48 h period with corresponding C max /MIC and AUC 0-24h /MIC ratios being greater than 10 and 125, respectively; the thresholds for optimal bactericidal efficacy. These findings identify the macromolecular prodrug platform as a potential therapeutic system to better treat alveolar intracellular infections such as F. tularensis, where positive patient outcomes

  3. Crystal pathologies in macromolecular crystallography.

    Science.gov (United States)

    Dauter, Zbigniew; Jaskólski, Mariusz

    Macromolecules, such as proteins or nucleic acids, form crystals with a large volume fraction of water, ~50% on average. Apart from typical physical defects and rather trivial poor quality problems, macromolecular crystals, as essentially any crystals, can also suffer from several kinds of pathologies, in which everything seems to be perfect, except that from the structural point of view the interpretation may be very difficult, sometimes even impossible. A frequent nuisance is pseudosymmetry, or non-crystallographic symmetry (NCS), which is particularly nasty when it has translational character. Lattice-translocation defects, also called order-disorder twinning (OD-twinning), occur when molecules are packed regularly in layers but the layers are stacked (without rotation) in two (or more) discrete modes, with a unique translocation vector. Crystal twinning arises when twin domains have different orientations, incompatible with the symmetry of the crystal structure. There are also crystals in which the periodic (lattice) order is broken or absent altogether. When the strict short-range translational order from one unit cell to the next is lost but the long-range order is restored by a periodic modulation, we have a modulated crystal structure. In quasicrystals (not observed for macromolecules yet), the periodic order (in 3D space) is lost completely and the diffraction pattern (which is still discrete) cannot be even indexed using three hkl indices. In addition, there are other physical defects and phenomena (such as high mosaicity, diffraction anisotropy, diffuse scattering, etc.) which make diffraction data processing and structure solution difficult or even impossible.

  4. Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Amninder S Virk

    2015-02-01

    Full Text Available Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction. Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

  5. International summer school on macromolecular crystallographic computing. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-08-01

    The School was the seventh in a series of International Union of Crystallography (IUCr) Crystallographic Symposia. The format of the School was formal lectures in the morning, tutorials in the afternoon, and software demonstrations and more lectures in the evening. The full program which left both the organizers and attendees exhausted, reflects the current state of excitement in the field of macromolecular structure determination using the technique of X-ray crystallography. The new and improved technologies and techniques described in these Proceedings are contributing to that growth and at the same time, as pointed out in the paper given by Sussman, creating challenges for the Protein Data Bank (PDB). As the School progressed, the authors were struck by the similarities to events which took place in small molecule crystallography beginning some 20 to 25 years ago. Growth then was fueled by the advent of new algorithms, affordable computer hardware, and good software. So it is today for macromolecular crystallography, but with the added bonus of the Internet which is changing how scientist conduct their research. Flack presented this view as part of his on-going contribution to how crystallographers use the Internet. After presentations discussing structures en masse they returned to the more traditional mode of presentation which parallels the determination of a single macromolecular structure: data collection -- phasing -- model building and visualization -- refinement.

  6. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  7. The design of macromolecular crystallography diffraction experiments

    International Nuclear Information System (INIS)

    Evans, Gwyndaf; Axford, Danny; Owen, Robin L.

    2011-01-01

    Thoughts about the decisions made in designing macromolecular X-ray crystallography experiments at synchrotron beamlines are presented. The measurement of X-ray diffraction data from macromolecular crystals for the purpose of structure determination is the convergence of two processes: the preparation of diffraction-quality crystal samples on the one hand and the construction and optimization of an X-ray beamline and end station on the other. Like sample preparation, a macromolecular crystallography beamline is geared to obtaining the best possible diffraction measurements from crystals provided by the synchrotron user. This paper describes the thoughts behind an experiment that fully exploits both the sample and the beamline and how these map into everyday decisions that users can and should make when visiting a beamline with their most precious crystals

  8. JBlulce Data Acquisition Software for Macromolecular Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    2010-06-01

    JBlulce (Java Beam Line Universal Integrated Configuration Environment is a data acquisition software for macromolecular crystallography conforming user interface of the SSRL Blulce that has become a de-factor standard in the field. Besides this interface conformity, JBlulce is a unique system in terms of architecture, speec, capability and osftware implementation. It features only two software layers, the JBlulce clients and the EPICS servers, as compared to three layers present in Blulc and most of similar systems. This layers reduction provides a faster communication with hardware and an easier access to advanced hardware capabilities like on-the-fly scanning. Then JBlulc clients are designed to operate in parallel with the other beamline controls which streamlines the tasks performed by staff such as beamline preparation, maitenance, audting and user assistance. Another distinction is the deployment of multiple plugins that can be written in any programming languag thus involving more staff into the development. further on, JBlulce makes use of unified motion controls allowing for easy scanning and optimizing of any beamline component. Finally, the graphic interface is implemented in Java making full use of rich Java libraries and Jave IDE for debugging. to compare, Blulce user interface is implemented with aging Tcl/tk language providing very restricted capabilities. JBlulce makes full use of the industrial power and wide drivers selection of EPICS in controlling hardware; all hardware commuication is routed via multiple EPICS servers residing on local area network. JBlulce also includes several EPICS State Notation servers aimed at making hardware communication more robust. Besides using EPICS for controlling hardware, JBlulce extensively uses EPICS databases for efficien communications between multiple instances of JBlulce clients and JBlulce pplugins that can run in parallel on different computers. All of the above makes JBlulce one of the biggest and most

  9. Peanut lectin crystallography and macromolecular structural studies ...

    Indian Academy of Sciences (India)

    2007-08-06

    Aug 6, 2007 ... Home; Journals; Journal of Biosciences; Volume 32; Issue 6. Peanut lectin crystallography and macromolecular structural studies in India. M Vijayan. Perspectives Volume 32 Issue 6 September 2007 pp 1059-1066. Fulltext. Click here to view fulltext PDF. Permanent link:

  10. Automated data collection for macromolecular crystallography.

    Science.gov (United States)

    Winter, Graeme; McAuley, Katherine E

    2011-09-01

    An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Status and prospects of macromolecular crystallography

    Indian Academy of Sciences (India)

    Also, computers with extremely large storage capacity and high comput- ing speeds became available at very low cost. These developments made macromolecular crystallogra- phy much like organic chemical crystallography, a task that could be almost completely automated. Initial studies on proteins were mostly on those.

  12. Conceptual design of novel IP-conveyor-belt Weissenberg-mode data-collection system with multi-readers for macromolecular crystallography. A comparison between Galaxy and Super Galaxy.

    Science.gov (United States)

    Sakabe, N; Sakabe, K; Sasaki, K

    2004-01-01

    Galaxy is a Weissenberg-type high-speed high-resolution and highly accurate fully automatic data-collection system using two cylindrical IP-cassettes each with a radius of 400 mm and a width of 450 mm. It was originally developed for static three-dimensional analysis using X-ray diffraction and was installed on bending-magnet beamline BL6C at the Photon Factory. It was found, however, that Galaxy was also very useful for time-resolved protein crystallography on a time scale of minutes. This has prompted us to design a new IP-conveyor-belt Weissenberg-mode data-collection system called Super Galaxy for time-resolved crystallography with improved time and crystallographic resolution over that achievable with Galaxy. Super Galaxy was designed with a half-cylinder-shaped cassette with a radius of 420 mm and a width of 690 mm. Using 1.0 A incident X-rays, these dimensions correspond to a maximum resolutions of 0.71 A in the vertical direction and 1.58 A in the horizontal. Upper and lower screens can be used to set the frame size of the recorded image. This function is useful not only to reduce the frame exchange time but also to save disk space on the data server. The use of an IP-conveyor-belt and many IP-readers make Super Galaxy well suited for time-resolved, monochromatic X-ray crystallography at a very intense third-generation SR beamline. Here, Galaxy and a conceptual design for Super Galaxy are described, and their suitability for use as data-collection systems for macromolecular time-resolved monochromatic X-ray crystallography are compared.

  13. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction of the c......Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction...... of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair...

  14. In situ macromolecular crystallography using microbeams.

    Science.gov (United States)

    Axford, Danny; Owen, Robin L; Aishima, Jun; Foadi, James; Morgan, Ann W; Robinson, James I; Nettleship, Joanne E; Owens, Raymond J; Moraes, Isabel; Fry, Elizabeth E; Grimes, Jonathan M; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S; Stuart, David I; Evans, Gwyndaf

    2012-05-01

    Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams. © 2012 International Union of Crystallography

  15. Topology evolution in macromolecular networks

    NARCIS (Netherlands)

    Kryven, I.

    2014-01-01

    Governed by various intermolecular forces, molecular networks tend to evolve from simple to very complex formations that have random structure. This randomness in the connectivity of the basic units can still be captured employing distributional description of the state of the system; the evolution

  16. Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet.

    Science.gov (United States)

    Pérez-Jiménez, Jara; Díaz-Rubio, M Elena; Saura-Calixto, Fulgencio

    2015-12-01

    Epidemiological and clinical studies show that diets with a high antioxidant capacity, such us those rich in plant food and beverages, are associated with significant decreases in the overall risk of cardiovascular disease or colorectal cancer. Current studies on dietary antioxidants and dietary antioxidant capacity focus exclusively on low molecular weight or soluble antioxidants (vitamins C and E, phenolic compounds and carotenoids), ignoring macromolecular antioxidants. These are polymeric phenolic compounds or polyphenols and carotenoids linked to plant food macromolecules that yield bioavailable metabolites by the action of the microbiota with significant effects either local and/or systemic after absorption. This study determined the antioxidant capacity of the Spanish Mediterranean diet including for the first time both soluble and macromolecular antioxidants. Antioxidant capacity and consumption data of the 54 most consumed plant foods and beverages were used. Results showed that macromolecular antioxidants are the major dietary antioxidants, contributing a 61% to the diet antioxidant capacity (8000 μmol Trolox, determined by ABTS method). The antioxidant capacity data for foods and beverages provided here may be used to estimate the dietary antioxidant capacity in different populations, where similar contributions of macromolecular antioxidants may be expected, and also to design antioxidant-rich diets. Including macromolecular antioxidants in mechanistic, intervention and observational studies on dietary antioxidants may contribute to a better understanding of the role of antioxidants in nutrition and health.

  17. PDBe: improved accessibility of macromolecular structure data from PDB and EMDB.

    Science.gov (United States)

    Velankar, Sameer; van Ginkel, Glen; Alhroub, Younes; Battle, Gary M; Berrisford, John M; Conroy, Matthew J; Dana, Jose M; Gore, Swanand P; Gutmanas, Aleksandras; Haslam, Pauline; Hendrickx, Pieter M S; Lagerstedt, Ingvar; Mir, Saqib; Fernandez Montecelo, Manuel A; Mukhopadhyay, Abhik; Oldfield, Thomas J; Patwardhan, Ardan; Sanz-García, Eduardo; Sen, Sanchayita; Slowley, Robert A; Wainwright, Michael E; Deshpande, Mandar S; Iudin, Andrii; Sahni, Gaurav; Salavert Torres, Jose; Hirshberg, Miriam; Mak, Lora; Nadzirin, Nurul; Armstrong, David R; Clark, Alice R; Smart, Oliver S; Korir, Paul K; Kleywegt, Gerard J

    2016-01-04

    The Protein Data Bank in Europe (http://pdbe.org) accepts and annotates depositions of macromolecular structure data in the PDB and EMDB archives and enriches, integrates and disseminates structural information in a variety of ways. The PDBe website has been redesigned based on an analysis of user requirements, and now offers intuitive access to improved and value-added macromolecular structure information. Unique value-added information includes lists of reviews and research articles that cite or mention PDB entries as well as access to figures and legends from full-text open-access publications that describe PDB entries. A powerful new query system not only shows all the PDB entries that match a given query, but also shows the 'best structures' for a given macromolecule, ligand complex or sequence family using data-quality information from the wwPDB validation reports. A PDBe RESTful API has been developed to provide unified access to macromolecular structure data available in the PDB and EMDB archives as well as value-added annotations, e.g. regarding structure quality and up-to-date cross-reference information from the SIFTS resource. Taken together, these new developments facilitate unified access to macromolecular structure data in an intuitive way for non-expert users and support expert users in analysing macromolecular structure data. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Distributed computing for macromolecular crystallography.

    Science.gov (United States)

    Krissinel, Evgeny; Uski, Ville; Lebedev, Andrey; Winn, Martyn; Ballard, Charles

    2018-02-01

    Modern crystallographic computing is characterized by the growing role of automated structure-solution pipelines, which represent complex expert systems utilizing a number of program components, decision makers and databases. They also require considerable computational resources and regular database maintenance, which is increasingly more difficult to provide at the level of individual desktop-based CCP4 setups. On the other hand, there is a significant growth in data processed in the field, which brings up the issue of centralized facilities for keeping both the data collected and structure-solution projects. The paradigm of distributed computing and data management offers a convenient approach to tackling these problems, which has become more attractive in recent years owing to the popularity of mobile devices such as tablets and ultra-portable laptops. In this article, an overview is given of developments by CCP4 aimed at bringing distributed crystallographic computations to a wide crystallographic community.

  19. Outrunning free radicals in room-temperature macromolecular crystallography

    International Nuclear Information System (INIS)

    Owen, Robin L.; Axford, Danny; Nettleship, Joanne E.; Owens, Raymond J.; Robinson, James I.; Morgan, Ann W.; Doré, Andrew S.; Lebon, Guillaume; Tate, Christopher G.; Fry, Elizabeth E.; Ren, Jingshan; Stuart, David I.; Evans, Gwyndaf

    2012-01-01

    A systematic increase in lifetime is observed in room-temperature protein and virus crystals through the use of reduced exposure times and a fast detector. A significant increase in the lifetime of room-temperature macromolecular crystals is reported through the use of a high-brilliance X-ray beam, reduced exposure times and a fast-readout detector. This is attributed to the ability to collect diffraction data before hydroxyl radicals can propagate through the crystal, fatally disrupting the lattice. Hydroxyl radicals are shown to be trapped in amorphous solutions at 100 K. The trend in crystal lifetime was observed in crystals of a soluble protein (immunoglobulin γ Fc receptor IIIa), a virus (bovine enterovirus serotype 2) and a membrane protein (human A 2A adenosine G-protein coupled receptor). The observation of a similar effect in all three systems provides clear evidence for a common optimal strategy for room-temperature data collection and will inform the design of future synchrotron beamlines and detectors for macromolecular crystallography

  20. Outrunning free radicals in room-temperature macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Robin L., E-mail: robin.owen@diamond.ac.uk; Axford, Danny [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); Nettleship, Joanne E.; Owens, Raymond J. [Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Robinson, James I.; Morgan, Ann W. [University of Leeds, Leeds LS9 7FT (United Kingdom); Doré, Andrew S. [Heptares Therapeutics Ltd, BioPark, Welwyn Garden City AL7 3AX (United Kingdom); Lebon, Guillaume; Tate, Christopher G. [MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH (United Kingdom); Fry, Elizabeth E.; Ren, Jingshan [The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Stuart, David I. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Evans, Gwyndaf [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom)

    2012-06-15

    A systematic increase in lifetime is observed in room-temperature protein and virus crystals through the use of reduced exposure times and a fast detector. A significant increase in the lifetime of room-temperature macromolecular crystals is reported through the use of a high-brilliance X-ray beam, reduced exposure times and a fast-readout detector. This is attributed to the ability to collect diffraction data before hydroxyl radicals can propagate through the crystal, fatally disrupting the lattice. Hydroxyl radicals are shown to be trapped in amorphous solutions at 100 K. The trend in crystal lifetime was observed in crystals of a soluble protein (immunoglobulin γ Fc receptor IIIa), a virus (bovine enterovirus serotype 2) and a membrane protein (human A{sub 2A} adenosine G-protein coupled receptor). The observation of a similar effect in all three systems provides clear evidence for a common optimal strategy for room-temperature data collection and will inform the design of future synchrotron beamlines and detectors for macromolecular crystallography.

  1. Progress in rational methods of cryoprotection in macromolecular crystallography

    International Nuclear Information System (INIS)

    Alcorn, Thomas; Juers, Douglas H.

    2010-01-01

    Measurements of the average thermal contractions (294→72 K) of 26 different cryosolutions are presented and discussed in conjunction with other recent advances in the rational design of protocols for cryogenic cooling in macromolecular crystallography. Cryogenic cooling of macromolecular crystals is commonly used for X-ray data collection both to reduce crystal damage from radiation and to gather functional information by cryogenically trapping intermediates. However, the cooling process can damage the crystals. Limiting cooling-induced crystal damage often requires cryoprotection strategies, which can involve substantial screening of solution conditions and cooling protocols. Here, recent developments directed towards rational methods for cryoprotection are described. Crystal damage is described in the context of the temperature response of the crystal as a thermodynamic system. As such, the internal and external parts of the crystal typically have different cryoprotection requirements. A key physical parameter, the thermal contraction, of 26 different cryoprotective solutions was measured between 294 and 72 K. The range of contractions was 2–13%, with the more polar cryosolutions contracting less. The potential uses of these results in the development of cryocooling conditions, as well as recent developments in determining minimum cryosolution soaking times, are discussed

  2. A public database of macromolecular diffraction experiments.

    Science.gov (United States)

    Grabowski, Marek; Langner, Karol M; Cymborowski, Marcin; Porebski, Przemyslaw J; Sroka, Piotr; Zheng, Heping; Cooper, David R; Zimmerman, Matthew D; Elsliger, Marc André; Burley, Stephen K; Minor, Wladek

    2016-11-01

    The low reproducibility of published experimental results in many scientific disciplines has recently garnered negative attention in scientific journals and the general media. Public transparency, including the availability of `raw' experimental data, will help to address growing concerns regarding scientific integrity. Macromolecular X-ray crystallography has led the way in requiring the public dissemination of atomic coordinates and a wealth of experimental data, making the field one of the most reproducible in the biological sciences. However, there remains no mandate for public disclosure of the original diffraction data. The Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) has been developed to archive raw data from diffraction experiments and, equally importantly, to provide related metadata. Currently, the database of our resource contains data from 2920 macromolecular diffraction experiments (5767 data sets), accounting for around 3% of all depositions in the Protein Data Bank (PDB), with their corresponding partially curated metadata. IRRMC utilizes distributed storage implemented using a federated architecture of many independent storage servers, which provides both scalability and sustainability. The resource, which is accessible via the web portal at http://www.proteindiffraction.org, can be searched using various criteria. All data are available for unrestricted access and download. The resource serves as a proof of concept and demonstrates the feasibility of archiving raw diffraction data and associated metadata from X-ray crystallographic studies of biological macromolecules. The goal is to expand this resource and include data sets that failed to yield X-ray structures in order to facilitate collaborative efforts that will improve protein structure-determination methods and to ensure the availability of `orphan' data left behind for various reasons by individual investigators and/or extinct structural genomics

  3. Celebrating macromolecular crystallography: A personal perspective

    Directory of Open Access Journals (Sweden)

    Abad-Zapatero, Celerino

    2015-04-01

    Full Text Available The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina, hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se

  4. Path Similarity Analysis: A Method for Quantifying Macromolecular Pathways.

    Directory of Open Access Journals (Sweden)

    Sean L Seyler

    2015-10-01

    Full Text Available Diverse classes of proteins function through large-scale conformational changes and various sophisticated computational algorithms have been proposed to enhance sampling of these macromolecular transition paths. Because such paths are curves in a high-dimensional space, it has been difficult to quantitatively compare multiple paths, a necessary prerequisite to, for instance, assess the quality of different algorithms. We introduce a method named Path Similarity Analysis (PSA that enables us to quantify the similarity between two arbitrary paths and extract the atomic-scale determinants responsible for their differences. PSA utilizes the full information available in 3N-dimensional configuration space trajectories by employing the Hausdorff or Fréchet metrics (adopted from computational geometry to quantify the degree of similarity between piecewise-linear curves. It thus completely avoids relying on projections into low dimensional spaces, as used in traditional approaches. To elucidate the principles of PSA, we quantified the effect of path roughness induced by thermal fluctuations using a toy model system. Using, as an example, the closed-to-open transitions of the enzyme adenylate kinase (AdK in its substrate-free form, we compared a range of protein transition path-generating algorithms. Molecular dynamics-based dynamic importance sampling (DIMS MD and targeted MD (TMD and the purely geometric FRODA (Framework Rigidity Optimized Dynamics Algorithm were tested along with seven other methods publicly available on servers, including several based on the popular elastic network model (ENM. PSA with clustering revealed that paths produced by a given method are more similar to each other than to those from another method and, for instance, that the ENM-based methods produced relatively similar paths. PSA applied to ensembles of DIMS MD and FRODA trajectories of the conformational transition of diphtheria toxin, a particularly challenging example

  5. In situ macromolecular crystallography using microbeams

    International Nuclear Information System (INIS)

    Axford, Danny; Owen, Robin L.; Aishima, Jun; Foadi, James; Morgan, Ann W.; Robinson, James I.; Nettleship, Joanne E.; Owens, Raymond J.; Moraes, Isabel; Fry, Elizabeth E.; Grimes, Jonathan M.; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S.; Stuart, David I.; Evans, Gwyndaf

    2012-01-01

    A sample environment for mounting crystallization trays has been developed on the microfocus beamline I24 at Diamond Light Source. The technical developments and several case studies are described. Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams

  6. EIGER detector: application in macromolecular crystallography.

    Science.gov (United States)

    Casanas, Arnau; Warshamanage, Rangana; Finke, Aaron D; Panepucci, Ezequiel; Olieric, Vincent; Nöll, Anne; Tampé, Robert; Brandstetter, Stefan; Förster, Andreas; Mueller, Marcus; Schulze-Briese, Clemens; Bunk, Oliver; Wang, Meitian

    2016-09-01

    The development of single-photon-counting detectors, such as the PILATUS, has been a major recent breakthrough in macromolecular crystallography, enabling noise-free detection and novel data-acquisition modes. The new EIGER detector features a pixel size of 75 × 75 µm, frame rates of up to 3000 Hz and a dead time as low as 3.8 µs. An EIGER 1M and EIGER 16M were tested on Swiss Light Source beamlines X10SA and X06SA for their application in macromolecular crystallography. The combination of fast frame rates and a very short dead time allows high-quality data acquisition in a shorter time. The ultrafine ϕ-slicing data-collection method is introduced and validated and its application in finding the optimal rotation angle, a suitable rotation speed and a sufficient X-ray dose are presented. An improvement of the data quality up to slicing at one tenth of the mosaicity has been observed, which is much finer than expected based on previous findings. The influence of key data-collection parameters on data quality is discussed.

  7. The role of macromolecular stability in desiccation tolerance

    NARCIS (Netherlands)

    Wolkers, W.F.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular

  8. Associative Pattern Recognition Through Macro-molecular Self-Assembly

    Science.gov (United States)

    Zhong, Weishun; Schwab, David J.; Murugan, Arvind

    2017-05-01

    We show that macro-molecular self-assembly can recognize and classify high-dimensional patterns in the concentrations of N distinct molecular species. Similar to associative neural networks, the recognition here leverages dynamical attractors to recognize and reconstruct partially corrupted patterns. Traditional parameters of pattern recognition theory, such as sparsity, fidelity, and capacity are related to physical parameters, such as nucleation barriers, interaction range, and non-equilibrium assembly forces. Notably, we find that self-assembly bears greater similarity to continuous attractor neural networks, such as place cell networks that store spatial memories, rather than discrete memory networks. This relationship suggests that features and trade-offs seen here are not tied to details of self-assembly or neural network models but are instead intrinsic to associative pattern recognition carried out through short-ranged interactions.

  9. Macromolecular organization of xyloglucan and cellulose in pea epicotyls

    International Nuclear Information System (INIS)

    Hayashi, T.; Maclachlan, G.

    1984-01-01

    Xyloglucan is known to occur widely in the primary cell walls of higher plants. This polysaccharide in most dicots possesses a cellulose-like main chain with three of every four consecutive residues substituted with xylose and minor addition of other sugars. Xyloglucan and cellulose metabolism is regulated by different processes; since different enzyme systems are probably required for the synthesis of their 1,4-β-linkages. A macromolecular complex composed of xyloglucan and cellulose only was obtained from elongating regions of etiolated pea stems. It was examined by light microscopy using iodine staining, by radioautography after labeling with [ 3 H]fructose, by fluorescence microscopy using a fluorescein-lectin (fructose-binding) as probe, and by electron microscopy after shadowing. The techniques all demonstrated that the macromolecule was present in files of cell shapes, referred to here as cell-wall ghosts, in which xyloglucan was localized both on and between the cellulose microfibrils

  10. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    International Nuclear Information System (INIS)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary; Ravelli, Raimond B. G.; Carmichael, Ian; Kneale, Geoff; McGeehan, John E.

    2015-01-01

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N 1 —C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses

  11. Challenges and Perspectives in the Macromolecular Flatland.

    Science.gov (United States)

    Servalli, Marco

    2017-06-28

    Polymer chemistry has recently welcomed a new addition to its field: the planar macromolecules known as two-dimensional polymers (2DPs). These topologically planar and crystalline monolayer covalent sheets are reminiscent of molecular fishermen's nets and apart from being conceptually very interesting for the field of macro-molecular chemistry, they also show some potential applications as novel 2D materials. This article reviews how the field has developed five years after the first 2DP was synthesised in 2012. After a brief historical introduction, the main synthetic approaches will be discussed providing concrete examples of 2DPs and highlighting the challenges associated with the synthesis and especially structural characterisation of these fascinating macro-molecules. Finally an overview on their potential applications such as membranes for gas separation, rewritable molecular paper and miniaturisation of optical devices will be presented.

  12. Modeling of System Families

    National Research Council Canada - National Science Library

    Feiler, Peter

    2007-01-01

    .... The Society of Automotive Engineers (SAE) Architecture Analysis & Design Language (AADL) is an industry-standard, architecture-modeling notation specifically designed to support a component- based approach to modeling embedded systems...

  13. Modelling Railway Interlocking Systems

    DEFF Research Database (Denmark)

    Lindegaard, Morten Peter; Viuf, P.; Haxthausen, Anne Elisabeth

    2000-01-01

    In this report we present a model of interlocking systems, and describe how the model may be validated by simulation. Station topologies are modelled by graphs in which the nodes denote track segments, and the edges denote connectivity for train traÆc. Points and signals are modelled by annotatio...

  14. On macromolecular refinement at subatomic resolution with interatomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V., E-mail: pafonine@lbl.gov; Grosse-Kunstleve, Ralf W.; Adams, Paul D. [Lawrence Berkeley National Laboratory, One Cyclotron Road, BLDG 64R0121, Berkeley, CA 94720 (United States); Lunin, Vladimir Y. [Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Pushchino 142290 (Russian Federation); Urzhumtsev, Alexandre [IGMBC, 1 Rue L. Fries, 67404 Illkirch and IBMC, 15 Rue R. Descartes, 67084 Strasbourg (France); Faculty of Sciences, Nancy University, 54506 Vandoeuvre-lès-Nancy (France); Lawrence Berkeley National Laboratory, One Cyclotron Road, BLDG 64R0121, Berkeley, CA 94720 (United States)

    2007-11-01

    Modelling deformation electron density using interatomic scatters is simpler than multipolar methods, produces comparable results at subatomic resolution and can easily be applied to macromolecules. A study of the accurate electron-density distribution in molecular crystals at subatomic resolution (better than ∼1.0 Å) requires more detailed models than those based on independent spherical atoms. A tool that is conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8–1.0 Å, the number of experimental data is insufficient for full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark data sets gave results that were comparable in quality with the results of multipolar refinement and superior to those for conventional models. Applications to several data sets of both small molecules and macromolecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  15. Macromolecular X-ray structure determination using weak, single-wavelength anomalous data

    Energy Technology Data Exchange (ETDEWEB)

    Bunkóczi, Gábor; McCoy, Airlie J.; Echols, Nathaniel; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Holton, James M.; Read, Randy J.; Terwilliger, Thomas C.

    2014-12-22

    We describe a likelihood-based method for determining the substructure of anomalously scattering atoms in macromolecular crystals that allows successful structure determination by single-wavelength anomalous diffraction (SAD) X-ray analysis with weak anomalous signal. With the use of partial models and electron density maps in searches for anomalously scattering atoms, testing of alternative values of parameters and parallelized automated model-building, this method has the potential to extend the applicability of the SAD method in challenging cases.

  16. RSMASS system model development

    International Nuclear Information System (INIS)

    Marshall, A.C.; Gallup, D.R.

    1998-01-01

    RSMASS system mass models have been used for more than a decade to make rapid estimates of space reactor power system masses. This paper reviews the evolution of the RSMASS models and summarizes present capabilities. RSMASS has evolved from a simple model used to make rough estimates of space reactor and shield masses to a versatile space reactor power system model. RSMASS uses unique reactor and shield models that permit rapid mass optimization calculations for a variety of space reactor power and propulsion systems. The RSMASS-D upgrade of the original model includes algorithms for the balance of the power system, a number of reactor and shield modeling improvements, and an automatic mass optimization scheme. The RSMASS-D suite of codes cover a very broad range of reactor and power conversion system options as well as propulsion and bimodal reactor systems. Reactor choices include in-core and ex-core thermionic reactors, liquid metal cooled reactors, particle bed reactors, and prismatic configuration reactors. Power conversion options include thermoelectric, thermionic, Stirling, Brayton, and Rankine approaches. Program output includes all major component masses and dimensions, efficiencies, and a description of the design parameters for a mass optimized system. In the past, RSMASS has been used as an aid to identify and select promising concepts for space power applications. The RSMASS modeling approach has been demonstrated to be a valuable tool for guiding optimization of the power system design; consequently, the model is useful during system design and development as well as during the selection process. An improved in-core thermionic reactor system model RSMASS-T is now under development. The current development of the RSMASS-T code represents the next evolutionary stage of the RSMASS models. RSMASS-T includes many modeling improvements and is planned to be more user-friendly. RSMASS-T will be released as a fully documented, certified code at the end of

  17. Systemic resilience model

    International Nuclear Information System (INIS)

    Lundberg, Jonas; Johansson, Björn JE

    2015-01-01

    It has been realized that resilience as a concept involves several contradictory definitions, both for instance resilience as agile adjustment and as robust resistance to situations. Our analysis of resilience concepts and models suggest that beyond simplistic definitions, it is possible to draw up a systemic resilience model (SyRes) that maintains these opposing characteristics without contradiction. We outline six functions in a systemic model, drawing primarily on resilience engineering, and disaster response: anticipation, monitoring, response, recovery, learning, and self-monitoring. The model consists of four areas: Event-based constraints, Functional Dependencies, Adaptive Capacity and Strategy. The paper describes dependencies between constraints, functions and strategies. We argue that models such as SyRes should be useful both for envisioning new resilience methods and metrics, as well as for engineering and evaluating resilient systems. - Highlights: • The SyRes model resolves contradictions between previous resilience definitions. • SyRes is a core model for envisioning and evaluating resilience metrics and models. • SyRes describes six functions in a systemic model. • They are anticipation, monitoring, response, recovery, learning, self-monitoring. • The model describes dependencies between constraints, functions and strategies

  18. An upper limit for macromolecular crowding effects

    Directory of Open Access Journals (Sweden)

    Miklos Andrew C

    2011-05-01

    Full Text Available Abstract Background Solutions containing high macromolecule concentrations are predicted to affect a number of protein properties compared to those properties in dilute solution. In cells, these macromolecular crowders have a large range of sizes and can occupy 30% or more of the available volume. We chose to study the stability and ps-ns internal dynamics of a globular protein whose radius is ~2 nm when crowded by a synthetic microgel composed of poly(N-isopropylacrylamide-co-acrylic acid with particle radii of ~300 nm. Results Our studies revealed no change in protein rotational or ps-ns backbone dynamics and only mild (~0.5 kcal/mol at 37°C, pH 5.4 stabilization at a volume occupancy of 70%, which approaches the occupancy of closely packing spheres. The lack of change in rotational dynamics indicates the absence of strong crowder-protein interactions. Conclusions Our observations are explained by the large size discrepancy between the protein and crowders and by the internal structure of the microgels, which provide interstitial spaces and internal pores where the protein can exist in a dilute solution-like environment. In summary, microgels that interact weakly with proteins do not strongly influence protein dynamics or stability because these large microgels constitute an upper size limit on crowding effects.

  19. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  20. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  1. Canadian macromolecular crystallography facility: a suite of fully automated beamlines.

    Science.gov (United States)

    Grochulski, Pawel; Fodje, Michel; Labiuk, Shaunivan; Gorin, James; Janzen, Kathryn; Berg, Russ

    2012-06-01

    The Canadian light source is a 2.9 GeV national synchrotron radiation facility located on the University of Saskatchewan campus in Saskatoon. The small-gap in-vacuum undulator illuminated beamline, 08ID-1, together with the bending magnet beamline, 08B1-1, constitute the Canadian Macromolecular Crystallography Facility (CMCF). The CMCF provides service to more than 50 Principal Investigators in Canada and the United States. Up to 25% of the beam time is devoted to commercial users and the general user program is guaranteed up to 55% of the useful beam time through a peer-review process. CMCF staff provides "Mail-In" crystallography service to users with the highest scored proposals. Both beamlines are equipped with very robust end-stations including on-axis visualization systems, Rayonix 300 CCD series detectors and Stanford-type robotic sample auto-mounters. MxDC, an in-house developed beamline control system, is integrated with a data processing module, AutoProcess, allowing full automation of data collection and data processing with minimal human intervention. Sample management and remote monitoring of experiments is enabled through interaction with a Laboratory Information Management System developed at the facility.

  2. The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.

    Directory of Open Access Journals (Sweden)

    Jiachen Wei

    Full Text Available In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.

  3. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    Oxygen Demand) flux and SS flux in the inlet to the WWTP. COD is measured by means of a UV absorption sensor while SS is measured by a turbidity sensor. These models include a description of the deposit of COD and SS amounts, respectively, in the sewer system, and the models can thus be used to quantify......In this thesis, models of pollution fluxes in the inlet to 2 Danish wastewater treatment plants (WWTPs) as well as of suspended solids (SS) concentrations in the aeration tanks of an alternating WWTP and in the effluent from the aeration tanks are developed. The latter model is furthermore used...... to analyze and quantify the effect of the Aeration Tank Settling (ATS) operating mode, which is used during rain events. Furthermore, the model is used to propose a control algorithm for the phase lengths during ATS operation. The models are mainly formulated as state space model in continuous time...

  4. AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery

    International Nuclear Information System (INIS)

    Tsai, Yingssu; McPhillips, Scott E.; González, Ana; McPhillips, Timothy M.; Zinn, Daniel; Cohen, Aina E.; Feese, Michael D.; Bushnell, David; Tiefenbrunn, Theresa; Stout, C. David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O.; Soltis, S. Michael

    2013-01-01

    New software has been developed for automating the experimental and data-processing stages of fragment-based drug discovery at a macromolecular crystallography beamline. A new workflow-automation framework orchestrates beamline-control and data-analysis software while organizing results from multiple samples. AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully

  5. The R-factor gap in macromolecular crystallography: an untapped potential for insights on accurate structures.

    Science.gov (United States)

    Holton, James M; Classen, Scott; Frankel, Kenneth A; Tainer, John A

    2014-09-01

    In macromolecular crystallography, the agreement between observed and predicted structure factors (Rcryst and Rfree ) is seldom better than 20%. This is much larger than the estimate of experimental error (Rmerge ). The difference between Rcryst and Rmerge is the R-factor gap. There is no such gap in small-molecule crystallography, for which calculated structure factors are generally considered more accurate than the experimental measurements. Perhaps the true noise level of macromolecular data is higher than expected? Or is the gap caused by inaccurate phases that trap refined models in local minima? By generating simulated diffraction patterns using the program MLFSOM, and including every conceivable source of experimental error, we show that neither is the case. Processing our simulated data yielded values that were indistinguishable from those of real data for all crystallographic statistics except the final Rcryst and Rfree . These values decreased to 3.8% and 5.5% for simulated data, suggesting that the reason for high R-factors in macromolecular crystallography is neither experimental error nor phase bias, but rather an underlying inadequacy in the models used to explain our observations. The present inability to accurately represent the entire macromolecule with both its flexibility and its protein-solvent interface may be improved by synergies between small-angle X-ray scattering, computational chemistry and crystallography. The exciting implication of our finding is that macromolecular data contain substantial hidden and untapped potential to resolve ambiguities in the true nature of the nanoscale, a task that the second century of crystallography promises to fulfill. Coordinates and structure factors for the real data have been submitted to the Protein Data Bank under accession 4tws. © 2014 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  6. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  7. Modeling Complex Systems

    International Nuclear Information System (INIS)

    Schreckenberg, M

    2004-01-01

    This book by Nino Boccara presents a compilation of model systems commonly termed as 'complex'. It starts with a definition of the systems under consideration and how to build up a model to describe the complex dynamics. The subsequent chapters are devoted to various categories of mean-field type models (differential and recurrence equations, chaos) and of agent-based models (cellular automata, networks and power-law distributions). Each chapter is supplemented by a number of exercises and their solutions. The table of contents looks a little arbitrary but the author took the most prominent model systems investigated over the years (and up until now there has been no unified theory covering the various aspects of complex dynamics). The model systems are explained by looking at a number of applications in various fields. The book is written as a textbook for interested students as well as serving as a comprehensive reference for experts. It is an ideal source for topics to be presented in a lecture on dynamics of complex systems. This is the first book on this 'wide' topic and I have long awaited such a book (in fact I planned to write it myself but this is much better than I could ever have written it!). Only section 6 on cellular automata is a little too limited to the author's point of view and one would have expected more about the famous Domany-Kinzel model (and more accurate citation!). In my opinion this is one of the best textbooks published during the last decade and even experts can learn a lot from it. Hopefully there will be an actualization after, say, five years since this field is growing so quickly. The price is too high for students but this, unfortunately, is the normal case today. Nevertheless I think it will be a great success! (book review)

  8. Modeling the earth system

    Energy Technology Data Exchange (ETDEWEB)

    Ojima, D. [ed.

    1992-12-31

    The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.

  9. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  10. Timely deposition of macromolecular structures is necessary for peer review

    International Nuclear Information System (INIS)

    Joosten, Robbie P.; Soueidan, Hayssam; Wessels, Lodewyk F. A.; Perrakis, Anastassis

    2013-01-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature

  11. Macromolecular Antioxidants and Dietary Fiber in Edible Seaweeds.

    Science.gov (United States)

    Sanz-Pintos, Nerea; Pérez-Jiménez, Jara; Buschmann, Alejandro H; Vergara-Salinas, José Rodrigo; Pérez-Correa, José Ricardo; Saura-Calixto, Fulgencio

    2017-02-01

    Seaweeds are rich in different bioactive compounds with potential uses in drugs, cosmetics and the food industry. The objective of this study was to analyze macromolecular antioxidants or nonextractable polyphenols, in several edible seaweed species collected in Chile (Gracilaria chilensis, Callophyllis concepcionensis, Macrocystis pyrifera, Scytosyphon lomentaria, Ulva sp. and Enteromorpha compressa), including their 1st HPLC characterization. Macromolecular antioxidants are commonly ignored in studies of bioactive compounds. They are associated with insoluble dietary fiber and exhibit significant biological activity, with specific features that are different from those of both dietary fiber and extractable polyphenols. We also evaluated extractable polyphenols and dietary fiber, given their relationship with macromolecular antioxidants. Our results show that macromolecular antioxidants are a major polyphenol fraction (averaging 42% to total polyphenol content), with hydroxycinnamic acids, hydroxybenzoic acids and flavonols being the main constituents. This fraction also showed remarkable antioxidant capacity, as determined by 2 complementary assays. The dietary fiber content was over 50% of dry weight, with some samples exhibiting the target proportionality between soluble and insoluble dietary fiber for adequate nutrition. Overall, our data show that seaweed could be an important source of commonly ignored macromolecular antioxidants. © 2017 Institute of Food Technologists®.

  12. Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm.

    Science.gov (United States)

    Imam, Zachary I; Kenyon, Laura E; Ashby, Grant; Nagib, Fatema; Mendicino, Morgan; Zhao, Chi; Gadok, Avinash K; Stachowiak, Jeanne C

    2017-10-01

    From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes. Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and

  13. Macromolecular crystallography beamline X25 at the NSLS

    International Nuclear Information System (INIS)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L.; Dvorak, Joseph; Flaks, Leon; LaMarra, Steven; Myers, Stuart F.; Orville, Allen M.; Robinson, Howard H.; Roessler, Christian G.; Schneider, Dieter K.; Shea-McCarthy, Grace; Skinner, John M.; Skinner, Michael; Soares, Alexei S.; Sweet, Robert M.; Berman, Lonny E.

    2014-01-01

    A description of the upgraded beamline X25 at the NSLS, operated by the PXRR and the Photon Sciences Directorate serving the Macromolecular Crystallography community, is presented. Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community

  14. Adaptation to high temperatures through macromolecular dynamics by neutron scattering.

    Science.gov (United States)

    Tehei, Moeava; Zaccai, Giuseppe

    2007-08-01

    Work on the relationship between hyperthermophile protein dynamics, stability and activity is reviewed. Neutron spectroscopy has been applied to measure and compare the macromolecular dynamics of various hyperthermophilic and mesophilic proteins, under different conditions. First, molecular dynamics have been analyzed for the hyperthermophile malate dehydrogenase from Methanococcus jannaschii and a mesophilic homologue, the lactate dehydrogenase from Oryctolagus cunniculus (rabbit) muscle. The neutron scattering approach has provided independent measurements of the global flexibility and structural resilience of each protein, and it has been demonstrated that macromolecular dynamics represents one of the molecular mechanisms of thermoadaptation. The resilience was found to be higher for the hyperthermophilic protein, thus ensuring similar flexibilities in both enzymes at their optimal activity temperature. Second, the neutron method has been developed to quantify the average macromolecular flexibility and resilience within the natural crowded environment of the cell, and mean macromolecular motions have been measured in vivo in psychrophile, mesophile, thermophile and hyperthermophile bacteria. The macromolecular resilience in bacteria was found to increase with adaptation to high temperatures, whereas flexibility was maintained within narrow limits, independent of physiological temperature for all cells in their active state. Third, macromolecular motions have been measured in free and immobilized dihydrofolate reductase from Escherichia coli. The immobilized mesophilic enzyme has increased stability and decreased activity, so that its properties are changed to resemble those of a thermophilic enzyme. Quasi-elastic neutron scattering measurements have also been performed to probe the protein motions. Compared to the free enzyme, the average height of the activation free energy barrier to local motions was found to be increased by 0.54 kcal.mol(-1) in the

  15. Information Systems Efficiency Model

    Directory of Open Access Journals (Sweden)

    Milos Koch

    2017-07-01

    Full Text Available This contribution discusses the basic concept of creating a new model for the efficiency and effectiveness assessment of company information systems. The present trends in this field are taken into account, and the attributes are retained of measuring the optimal solutions for a company’s ICT (the implementation, functionality, service, innovations, safety, relationships, costs, etc.. The proposal of a new model of assessment comes from our experience with formerly implemented and employed methods, methods which we have modified in time and adapted to companies’ needs but also to the necessaries of our research that has been done through the ZEFIS portal. The most noteworthy of them is the HOS method that we have discussed in a number of forums. Its main feature is the fact that it respects the complexity of an information system in correlation with the balanced state of its individual parts.

  16. A sensor for quantification of macromolecular crowding in living cells

    NARCIS (Netherlands)

    Boersma, Arnold J; Zuhorn, Inge S; Poolman, Bert

    Macromolecular crowding in cells influences processes such as folding, association and diffusion of proteins and polynucleic acids. Direct spatiotemporal readout of crowding would be a powerful approach for unraveling the structure of the cytoplasm and determining the impact of excluded volume on

  17. The effect of macromolecular crowding on the electrostatic component of barnase-barstar binding: a computational, implicit solvent-based study.

    Directory of Open Access Journals (Sweden)

    Helena W Qi

    Full Text Available Macromolecular crowding within the cell can impact both protein folding and binding. Earlier models of cellular crowding focused on the excluded volume, entropic effect of crowding agents, which generally favors compact protein states. Recently, other effects of crowding have been explored, including enthalpically-related crowder-protein interactions and changes in solvation properties. In this work, we explore the effects of macromolecular crowding on the electrostatic desolvation and solvent-screened interaction components of protein-protein binding. Our simple model enables us to focus exclusively on the electrostatic effects of water depletion on protein binding due to crowding, providing us with the ability to systematically analyze and quantify these potentially intuitive effects. We use the barnase-barstar complex as a model system and randomly placed, uncharged spheres within implicit solvent to model crowding in an aqueous environment. On average, we find that the desolvation free energy penalties incurred by partners upon binding are lowered in a crowded environment and solvent-screened interactions are amplified. At a constant crowder density (fraction of total available volume occupied by crowders, this effect generally increases as the radius of model crowders decreases, but the strength and nature of this trend can depend on the water probe radius used to generate the molecular surface in the continuum model. In general, there is huge variation in desolvation penalties as a function of the random crowder positions. Results with explicit model crowders can be qualitatively similar to those using a lowered "effective" solvent dielectric to account for crowding, although the "best" effective dielectric constant will likely depend on multiple system properties. Taken together, this work systematically demonstrates, quantifies, and analyzes qualitative intuition-based insights into the effects of water depletion due to crowding on the

  18. Phase behaviour of macromolecular liquid crystalline materials. Computational studies at the molecular level

    International Nuclear Information System (INIS)

    Stimson, Lorna M.

    2003-01-01

    Molecular simulations provide an increasingly useful insight into the static and dynamic characteristics of materials. In this thesis molecular simulations of macro-molecular liquid crystalline materials are reported. The first liquid crystalline material that has been investigated is a side chain liquid crystal polymer (SCLCP). In this study semi-atomistic molecular dynamics simulations have been conducted at a range of temperatures and an aligning potential has been applied to mimic the effect of a magnetic field. In cooling the SCLCP from an isotropic melt, microphase separation was observed yielding a domain structure. The application of a magnetic field to this structure aligns the domains producing a stable smectic mesophase. This is the first study in which mesophases have been observed using an off-lattice model of a SCLCP. The second material that has been investigated is a dendrimer with terminal mesogenic functionalization. Here, a multi-scale approach has been taken with Monte Carlo studies of a single dendrimer molecule in the gas phase at the atomistic level, semi-atomistic molecular dynamics of a single molecule in liquid crystalline solvents and a coarse-grained molecular dynamics study of the dendrimer in the bulk. The coarse-grained model has been developed and parameterized using the results of the atomistic and semi-atomistic work. The single molecule studies showed that the liquid crystalline dendrimer was able to change its structure by conformational changes in the flexible chains that link the mesogenic groups to the core. Structural change was seen under the application of a mean field ordering potential in the gas phase, and in the presence of liquid crystalline solvents. No liquid crystalline phases were observed for the bulk phase studies of the coarse-grained model. However, when the length of the mesogenic units was increased there was some evidence for microphase separation in these systems. (author)

  19. Terminology and nomenclature for macromolecular rotaxanes and pseudorotaxanes (IUPAC Recommendations 2012)

    Czech Academy of Sciences Publication Activity Database

    Vohlídal, J.; Wilks, E. S.; Yerin, A.; Fradet, A.; Hellwich, K. H.; Hodge, P.; Kahovec, Jaroslav; Mormann, W.; Stepto, R. F. T.

    2012-01-01

    Roč. 84, č. 10 (2012), s. 2135-2165 ISSN 0033-4545 Institutional research plan: CEZ:AV0Z40500505 Keywords : IUPAC Chemical Nomenclature and Structure Representation Division * macromolecular pseudorotaxanes * macromolecular rotaxanes Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.386, year: 2012

  20. The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

    Science.gov (United States)

    Rajapaksha Mudalige, Ajith Rathnaweera

    Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied. We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl-alpha-glucoside (alpha-MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%. SAS coupled with osmotic pressure measurements allowed us to estimate a compressibility modulus for SOD. We believe this to be the first time the osmotic compressibility of a protein complex was measured. Molecular Dynamics (MD) simulations are widely used to obtain insights on biomolecular processes. However, it is not clear whether MD is capable of predicting subtle effects of macromolecular crowding. We used our experimentally observed compressibility of SOD to evaluate the ability of MD to predict macromolecular crowding. Effects of macromolecular crowding due to PEG on SOD were modeled using an all atom MD simulation with the CHARMM forcefield and the crystallographically resolved structures of SOD and PEG. Two parallel MD simulations were performed for SOD in water and SOD in 40% PEG for over 150~ns. Over the period of the simulation the SOD structure in 40

  1. AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery.

    Science.gov (United States)

    Tsai, Yingssu; McPhillips, Scott E; González, Ana; McPhillips, Timothy M; Zinn, Daniel; Cohen, Aina E; Feese, Michael D; Bushnell, David; Tiefenbrunn, Theresa; Stout, C David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O; Soltis, S Michael

    2013-05-01

    AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully demonstrated. This workflow was run once on the same 96 samples that the group had examined manually and the workflow cycled successfully through all of the samples, collected data from the same samples that were selected manually and located the same peaks of unmodeled density in the resulting difference Fourier

  2. Non-contact luminescence lifetime cryothermometry for macromolecular crystallography.

    Science.gov (United States)

    Mykhaylyk, V B; Wagner, A; Kraus, H

    2017-05-01

    Temperature is a very important parameter when aiming to minimize radiation damage to biological samples during experiments that utilize intense ionizing radiation. A novel technique for remote, non-contact, in situ monitoring of the protein crystal temperature has been developed for the new I23 beamline at the Diamond Light Source, a facility dedicated to macromolecular crystallography (MX) with long-wavelength X-rays. The temperature is derived from the temperature-dependent decay time constant of luminescence from a minuscule scintillation sensor (<0.05 mm 3 ) located in very close proximity to the sample under test. In this work the underlying principle of cryogenic luminescence lifetime thermometry is presented, the features of the detection method and the choice of temperature sensor are discussed, and it is demonstrated how the temperature monitoring system was integrated within the viewing system of the endstation used for the visualization of protein crystals. The thermometry system was characterized using a Bi 4 Ge 3 O 12 crystal scintillator that exhibits good responsivity of the decay time constant as a function of temperature over a wide range (8-270 K). The scintillation sensor was calibrated and the uncertainty of the temperature measurements over the primary operation temperature range of the beamline (30-150 K) was assessed to be ±1.6 K. It has been shown that the temperature of the sample holder, measured using the luminescence sensor, agrees well with the expected value. The technique was applied to characterize the thermal performance of different sample mounts that have been used in MX experiments at the I23 beamline. The thickness of the mount is shown to have the greatest impact upon the temperature distribution across the sample mount. Altogether, these tests and findings demonstrate the usefulness of the thermometry system in highlighting the challenges that remain to be addressed for the in-vacuum MX experiment to become a

  3. Beamline AR-NW12A: high-throughput beamline for macromolecular crystallography at the Photon Factory.

    Science.gov (United States)

    Chavas, L M G; Matsugaki, N; Yamada, Y; Hiraki, M; Igarashi, N; Suzuki, M; Wakatsuki, S

    2012-05-01

    AR-NW12A is an in-vacuum undulator beamline optimized for high-throughput macromolecular crystallography experiments as one of the five macromolecular crystallography (MX) beamlines at the Photon Factory. This report provides details of the beamline design, covering its optical specifications, hardware set-up, control software, and the latest developments for MX experiments. The experimental environment presents state-of-the-art instrumentation for high-throughput projects with a high-precision goniometer with an adaptable goniometer head, and a UV-light sample visualization system. Combined with an efficient automounting robot modified from the SSRL SAM system, a remote control system enables fully automated and remote-access X-ray diffraction experiments.

  4. Macromolecular metamorphosis via stimulus-induced transformations of polymer architecture.

    Science.gov (United States)

    Sun, Hao; Kabb, Christopher P; Dai, Yuqiong; Hill, Megan R; Ghiviriga, Ion; Bapat, Abhijeet P; Sumerlin, Brent S

    2017-08-01

    Macromolecular architecture plays a pivotal role in determining the properties of polymers. When designing polymers for specific applications, it is not only the size of a macromolecule that must be considered, but also its shape. In most cases, the topology of a polymer is a static feature that is inalterable once synthesized. Using reversible-covalent chemistry to prompt the disconnection of chemical bonds and the formation of new linkages in situ, we report polymers that undergo dramatic topological transformations via a process we term macromolecular metamorphosis. Utilizing this technique, a linear amphiphilic block copolymer or hyperbranched polymer undergoes 'metamorphosis' into comb, star and hydrophobic block copolymer architectures. This approach was extended to include a macroscopic gel which transitioned from a densely and covalently crosslinked network to one with larger distances between the covalent crosslinks when heated. These architectural transformations present an entirely new approach to 'smart' materials.

  5. Macromolecular metamorphosis via stimulus-induced transformations of polymer architecture

    Science.gov (United States)

    Sun, Hao; Kabb, Christopher P.; Dai, Yuqiong; Hill, Megan R.; Ghiviriga, Ion; Bapat, Abhijeet P.; Sumerlin, Brent S.

    2017-08-01

    Macromolecular architecture plays a pivotal role in determining the properties of polymers. When designing polymers for specific applications, it is not only the size of a macromolecule that must be considered, but also its shape. In most cases, the topology of a polymer is a static feature that is inalterable once synthesized. Using reversible-covalent chemistry to prompt the disconnection of chemical bonds and the formation of new linkages in situ, we report polymers that undergo dramatic topological transformations via a process we term macromolecular metamorphosis. Utilizing this technique, a linear amphiphilic block copolymer or hyperbranched polymer undergoes 'metamorphosis' into comb, star and hydrophobic block copolymer architectures. This approach was extended to include a macroscopic gel which transitioned from a densely and covalently crosslinked network to one with larger distances between the covalent crosslinks when heated. These architectural transformations present an entirely new approach to 'smart' materials.

  6. Impact of synchrotron radiation on macromolecular crystallography: a personal view

    Science.gov (United States)

    Dauter, Zbigniew; Jaskolski, Mariusz; Wlodawer, Alexander

    2010-01-01

    The introduction of synchrotron radiation sources almost four decades ago has led to a revolutionary change in the way that diffraction data from macromolecular crystals are being collected. Here a brief history of the development of methodologies that took advantage of the availability of synchrotron sources are presented, and some personal experiences with the utilization of synchrotrons in the early days are recalled. PMID:20567074

  7. Towards a compact and precise sample holder for macromolecular crystallography.

    Science.gov (United States)

    Papp, Gergely; Rossi, Christopher; Janocha, Robert; Sorez, Clement; Lopez-Marrero, Marcos; Astruc, Anthony; McCarthy, Andrew; Belrhali, Hassan; Bowler, Matthew W; Cipriani, Florent

    2017-10-01

    Most of the sample holders currently used in macromolecular crystallography offer limited storage density and poor initial crystal-positioning precision upon mounting on a goniometer. This has now become a limiting factor at high-throughput beamlines, where data collection can be performed in a matter of seconds. Furthermore, this lack of precision limits the potential benefits emerging from automated harvesting systems that could provide crystal-position information which would further enhance alignment at beamlines. This situation provided the motivation for the development of a compact and precise sample holder with corresponding pucks, handling tools and robotic transfer protocols. The development process included four main phases: design, prototype manufacture, testing with a robotic sample changer and validation under real conditions on a beamline. Two sample-holder designs are proposed: NewPin and miniSPINE. They share the same robot gripper and allow the storage of 36 sample holders in uni-puck footprint-style pucks, which represents 252 samples in a dry-shipping dewar commonly used in the field. The pucks are identified with human- and machine-readable codes, as well as with radio-frequency identification (RFID) tags. NewPin offers a crystal-repositioning precision of up to 10 µm but requires a specific goniometer socket. The storage density could reach 64 samples using a special puck designed for fully robotic handling. miniSPINE is less precise but uses a goniometer mount compatible with the current SPINE standard. miniSPINE is proposed for the first implementation of the new standard, since it is easier to integrate at beamlines. An upgraded version of the SPINE sample holder with a corresponding puck named SPINEplus is also proposed in order to offer a homogenous and interoperable system. The project involved several European synchrotrons and industrial companies in the fields of consumables and sample-changer robotics. Manual handling of mini

  8. Application of complex macromolecular architectures for advanced microelectronic materials.

    Science.gov (United States)

    Hedrick, James L; Magbitang, Teddie; Connor, Eric F; Glauser, Thierry; Volksen, Willi; Hawker, Craig J; Lee, Victor Y; Miller, Robert D

    2002-08-02

    The distinctive features of well-defined, three-dimensional macromolecules with topologies designed to enhance solubility and amplify end-group functionality facilitated nanophase morphologies in mixtures with organosilicates and ultimately nanoporous organosilicate networks. Novel macromolecular architectures including dendritic and star-shaped polymers and organic nanoparticles were prepared by a modular approach from several libraries of building blocks including various generations of dendritic initiators and dendrons, selectively placed to amplify functionality and/or arm number, coupled with living polymerization techniques. Mixtures of an organosilicate and the macromolecular template were deposited, cured, and the phase separation of the organic component, organized the vitrifying organosilicate into nanostructures. Removal of the sacrificial macromolecular template, also denoted as porogen, by thermolysis, yielded the desired nanoporous organosilicate, and the size scale of phase separation was strongly dependent on the chain topology. These materials were designed for use as interlayer, ultra-low dielectric insulators for on-chip applications with dielectric constant values as low as 1.5. The porogen design, chemistry and role of polymer architecture on hybrid and pore morphology will be emphasized.

  9. Cryo-Electron Tomography for Structural Characterization of Macromolecular Complexes

    Science.gov (United States)

    Cope, Julia; Heumann, John; Hoenger, Andreas

    2011-01-01

    Cryo-electron tomography (cryo-ET) is an emerging 3-D reconstruction technology that combines the principles of tomographic 3-D reconstruction with the unmatched structural preservation of biological material embedded in vitreous ice. Cryo-ET is particularly suited to investigating cell-biological samples and large macromolecular structures that are too polymorphic to be reconstructed by classical averaging-based 3-D reconstruction procedures. This unit aims to make cryo-ET accessible to newcomers and discusses the specialized equipment required, as well as the relevant advantages and hurdles associated with sample preparation by vitrification and cryo-ET. Protocols describe specimen preparation, data recording and 3-D data reconstruction for cryo-ET, with a special focus on macromolecular complexes. A step-by-step procedure for specimen vitrification by plunge freezing is provided, followed by the general practicalities of tilt-series acquisition for cryo-ET, including advice on how to select an area appropriate for acquiring a tilt series. A brief introduction to the underlying computational reconstruction principles applied in tomography is described, along with instructions for reconstructing a tomogram from cryo-tilt series data. Finally, a method is detailed for extracting small subvolumes containing identical macromolecular structures from tomograms for alignment and averaging as a means to increase the signal-to-noise ratio and eliminate missing wedge effects inherent in tomographic reconstructions. PMID:21842467

  10. Macromolecular composition and drug-loading effect on the delivery of paclitaxel and folic acid from acrylic matrices.

    Science.gov (United States)

    Gagliardi, M; Silvestri, D; Cristallini, C

    2010-08-01

    Drug delivery systems based on synthetic polymers are widely employed in the treatment of several pathologies. In particular, the use of implantable devices able to release one or more active principles in a topic site with a controlled delivery kinetic represents an important improvement in this field. However, the release kinetic, that could be affected by different parameters, like polymer composition or chemical nature and initial drug loading, represents one of the problems related to the implantation of delivery systems. In this study, acrylic membranes with different macromolecular composition were prepared and studied analyzing delivery kinetic properties. Drug delivery systems were prepared using as matrix the copolymer poly(methylmethacrylate-co-butylmethacrylate) in three different compositions and folic acid (less hydrophobic) or Paclitaxel (more hydrophobic) as drugs, to evaluate the effect of macromolecular composition and hydrophilicity degree on the release properties. In addition, the effect of the initial drug loading was considered, loading drug delivery systems with four different initial drug percentages. Results showed a direct dependence of kinetics from macromolecular composition, hydrophilicity degree of solutes, and initial drug loading, allowing one to conclude that it is possible to design and to develop drug delivery systems starting from poly(methylmethacrylate-co-butylmethacrylate) matrices with specific properties by varying these three parameters.

  11. Dynamics simulations for engineering macromolecular interactions

    Science.gov (United States)

    Robinson-Mosher, Avi; Shinar, Tamar; Silver, Pamela A.; Way, Jeffrey

    2013-06-01

    The predictable engineering of well-behaved transcriptional circuits is a central goal of synthetic biology. The artificial attachment of promoters to transcription factor genes usually results in noisy or chaotic behaviors, and such systems are unlikely to be useful in practical applications. Natural transcriptional regulation relies extensively on protein-protein interactions to insure tightly controlled behavior, but such tight control has been elusive in engineered systems. To help engineer protein-protein interactions, we have developed a molecular dynamics simulation framework that simplifies features of proteins moving by constrained Brownian motion, with the goal of performing long simulations. The behavior of a simulated protein system is determined by summation of forces that include a Brownian force, a drag force, excluded volume constraints, relative position constraints, and binding constraints that relate to experimentally determined on-rates and off-rates for chosen protein elements in a system. Proteins are abstracted as spheres. Binding surfaces are defined radially within a protein. Peptide linkers are abstracted as small protein-like spheres with rigid connections. To address whether our framework could generate useful predictions, we simulated the behavior of an engineered fusion protein consisting of two 20 000 Da proteins attached by flexible glycine/serine-type linkers. The two protein elements remained closely associated, as if constrained by a random walk in three dimensions of the peptide linker, as opposed to showing a distribution of distances expected if movement were dominated by Brownian motion of the protein domains only. We also simulated the behavior of fluorescent proteins tethered by a linker of varying length, compared the predicted Förster resonance energy transfer with previous experimental observations, and obtained a good correspondence. Finally, we simulated the binding behavior of a fusion of two ligands that could

  12. CROW for large scale macromolecular simulations.

    Science.gov (United States)

    Hodoscek, Milan; Borstnik, Urban; Janezic, Dusanka

    2002-01-01

    CROW (Columns and Rows Of Workstations - http://www.sicmm.org/crow/) is a parallel computer cluster based on the Beowulf (http://www.beowulf.org/) idea, modified to support a larger number of processors. Its architecture is based on point-to-point network architecture, which does not require the use of any network switching equipment in the system. Thus, the cost is lower, and there is no degradation in network performance even for a larger number of processors.

  13. Aging changes of macromolecular synthesis in the digestive organs of mice as revealed by microscopic radioautography and X-ray microanalysis

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu Univ., Matsumoto (Japan). School of Medicine. Dept. of Anatomy and Cell Biology]. E-mail: nagatas@po.cnet.ne.jp

    2002-07-01

    For the purpose of elucidating the aging changes of macromolecular synthesis such as DNA, RNA, proteins, glycoproteins, glycides and lipids in various organ systems of experimental animals, we have studied the digestive organs of aging mice and rats as a series of systematic studies using light and electron microscopic radioautography after incorporations with macromolecular precursors. The experimental animals mainly used were ddY strain mice at various aging groups from embryo to postnatal days 1 and 3, weeks 1 and 2, months 1, 2, 6, 12 up to 2 year senescent stages as well as several groups of adult Wistar rats. The animals were injected with such macromolecular precursors as {sup 3}H - thymidine for DNA, {sup 3}H-uridine for RNA, {sup 3}H-leucine and {sup 3}H proline for proteins, {sup 35}SO{sub 4} for glycoproteins, {sup 3} H-glucosamine for glucides and {sup 3}H-glycerol for lipids. The results demonstrated that these precursors were incorporated into various cell types in the oral cavity, the salivary glands, the esophagus, the stomach, the small and large intestines, the liver and the pancreas at various ages from perinatal to juvenile, mature and senescent stages, showing specific patterns of macromolecular synthesis. It is concluded that these specific patterns of macromolecular synthesis in respective cell types demonstrated the organ specificity of aging of animals. (author)

  14. Modeling and estimating system availability

    International Nuclear Information System (INIS)

    Gaver, D.P.; Chu, B.B.

    1976-11-01

    Mathematical models to infer the availability of various types of more or less complicated systems are described. The analyses presented are probabilistic in nature and consist of three parts: a presentation of various analytic models for availability; a means of deriving approximate probability limits on system availability; and a means of statistical inference of system availability from sparse data, using a jackknife procedure. Various low-order redundant systems are used as examples, but extension to more complex systems is not difficult

  15. A facile metal-free "grafting-from" route from acrylamide-based substrate toward complex macromolecular combs

    KAUST Repository

    Zhao, Junpeng

    2013-01-01

    High-molecular-weight poly(N,N-dimethylacrylamide-co-acrylamide) was used as a model functional substrate to investigate phosphazene base (t-BuP 4)-promoted metal-free anionic graft polymerization utilizing primary amide moieties as initiating sites. The (co)polymerization of epoxides was proven to be effective, leading to macromolecular combs with side chains being single- or double-graft homopolymer, block copolymer and statistical copolymer. © 2013 The Royal Society of Chemistry.

  16. Pulsatile Gating of Giant Vesicles Containing Macromolecular Crowding Agents Induced by Colligative Nonideality.

    Science.gov (United States)

    Su, Wan-Chih; Gettel, Douglas L; Chabanon, Morgan; Rangamani, Padmini; Parikh, Atul N

    2018-01-17

    The ability of large macromolecules to exhibit nontrivial deviations in colligative properties of their aqueous solutions is well-appreciated in polymer physics. Here, we show that this colligative nonideality subjects giant lipid vesicles containing inert macromolecular crowding agents to osmotic pressure differentials when bathed in small-molecule osmolytes at comparable concentrations. The ensuing influx of water across the semipermeable membrane induces characteristic swell-burst cycles: here, cyclical and damped oscillations in size, tension, and membrane phase separation occur en route to equilibration. Mediated by synchronized formation of transient pores, these cycles orchestrate pulsewise ejection of macromolecules from the vesicular interior reducing the osmotic differential in a stepwise manner. These experimental findings are fully corroborated by a theoretical model derived by explicitly incorporating the contributions of the solution viscosity, solute diffusivity, and the colligative nonideality of the osmotic pressure in a previously reported continuum description. Simulations based on this model account for the differences in the details of the noncolligatively induced swell-burst cycles, including numbers and periods of the repeating cycles, as well as pore lifetimes. Taken together, our observations recapitulate behaviors of vesicles and red blood cells experiencing sudden osmotic shocks due to large (hundreds of osmolars) differences in the concentrations of small molecule osmolytes and link intravesicular macromolecular crowding with membrane remodeling. They further suggest that any tendency for spontaneous overcrowding in single giant vesicles is opposed by osmotic stresses and requires independent specific interactions, such as associative chemical interactions or those between the crowders and the membrane boundary.

  17. Resolving macromolecular structures from electron cryo-tomography data using subtomogram averaging in RELION.

    Science.gov (United States)

    Bharat, Tanmay A M; Scheres, Sjors H W

    2016-11-01

    Electron cryo-tomography (cryo-ET) is a technique that is used to produce 3D pictures (tomograms) of complex objects such as asymmetric viruses, cellular organelles or whole cells from a series of tilted electron cryo-microscopy (cryo-EM) images. Averaging of macromolecular complexes found within tomograms is known as subtomogram averaging, and this technique allows structure determination of macromolecular complexes in situ. Subtomogram averaging is also gaining in popularity for the calculation of initial models for single-particle analysis. We describe herein a protocol for subtomogram averaging from cryo-ET data using the RELION software (http://www2.mrc-lmb.cam.ac.uk/relion). RELION was originally developed for cryo-EM single-particle analysis, and the subtomogram averaging approach presented in this protocol has been implemented in the existing workflow for single-particle analysis so that users may conveniently tap into existing capabilities of the RELION software. We describe how to calculate 3D models for the contrast transfer function (CTF) that describe the transfer of information in the imaging process, and we illustrate the results of classification and subtomogram averaging refinement for cryo-ET data of purified hepatitis B capsid particles and Saccharomyces cerevisiae 80S ribosomes. Using the steps described in this protocol, along with the troubleshooting and optimization guidelines, high-resolution maps can be obtained in which secondary structure elements are resolved subtomogram.

  18. Neutron Crystallography for Macromolecular Structure Analysis

    Science.gov (United States)

    Kuroki, Ryota

    Hydrogen atoms in proteins as well as protein-bound water molecules play a significant role in many chemical reaction processes in living systems, such as catalytic reaction and molecular recognition. Neutron crystallography is a powerful tool to identify locations of light atoms like hydrogen. In the field of neutron crystallography, the development of diffractometers and techniques for preparation and crystallization of target samples has been developed to complement the low flux of neutron sources. In Japan, single-crystal diffractometers named BIX-3 and BIX-4 have been developed, and contribute to the effective collection of neutron diffraction data. Recent developments on the complementary use of neutron and X-ray diffraction data have begun solving previously undetermined problems of protein function. Further efforts to acquire higher measurement performance are now in progress to increase the application of neutron crystallographic studies.

  19. Modelling of reverberation enhancement systems

    OpenAIRE

    ROUCH , Jeremy; Schmich , Isabelle; Galland , Marie-Annick

    2012-01-01

    International audience; Electroacoustic enhancement systems are increasingly specified by acoustic consultants to address the requests for a multi-purpose use of performance halls. However, there is still a lack of simple models to predict the effect induced by these systems on the acoustic field. Two models are introduced to establish the impulse responses of a room equipped with a reverberation enhancement system. These models are based on passive impulse responses according to the modified...

  20. MODELLING OF MATERIAL FLOW SYSTEMS

    OpenAIRE

    PÉTER TELEK

    2012-01-01

    Material flow systems are in generally very complex processes. During design, building and operation of complex systems there are many different problems. If these complex processes can be described in a simple model, the tasks will be clearer, better adaptable and easier solvable. As the material flow systems are very different, so using models is a very important aid to create uniform methods and solutions. This paper shows the details of the application possibilities of modelling in the ma...

  1. Dynamic Modeling of ALS Systems

    Science.gov (United States)

    Jones, Harry

    2002-01-01

    The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.

  2. Modeling soft interface dominated systems

    NARCIS (Netherlands)

    Lamorgese, A.; Mauri, R.; Sagis, L.M.C.

    2017-01-01

    The two main continuum frameworks used for modeling the dynamics of soft multiphase systems are the Gibbs dividing surface model, and the diffuse interface model. In the former the interface is modeled as a two dimensional surface, and excess properties such as a surface density, or surface energy

  3. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  4. From Numeric Models to Granular System Modeling

    Directory of Open Access Journals (Sweden)

    Witold Pedrycz

    2015-03-01

    To make this study self-contained, we briefly recall the key concepts of granular computing and demonstrate how this conceptual framework and its algorithmic fundamentals give rise to granular models. We discuss several representative formal setups used in describing and processing information granules including fuzzy sets, rough sets, and interval calculus. Key architectures of models dwell upon relationships among information granules. We demonstrate how information granularity and its optimization can be regarded as an important design asset to be exploited in system modeling and giving rise to granular models. With this regard, an important category of rule-based models along with their granular enrichments is studied in detail.

  5. Macromolecular Diffusion in Dynamic Polymer Nanocomposite

    Science.gov (United States)

    Lin, Chia-Chun; Cargnello, Matteo; Clarke, Nigel; Winey, Karen; Composto, Russell

    2015-03-01

    We consider diffusion of tracer polymers in the presence of mobile nanoparticles in polymer nanocomposites (PNCs). These nanoparticles are mobile on the time scale of polymer diffusion and have dimensions less than the entanglement mesh size (i.e., tube diameter). The PNC consists of titanium dioxide nanorods (NR, diameter=4.5nm; length=30.1nm) grafted with phenyl groups uniformly dispersed in a polystyrene (P=650kg/mol; tube diameter=8nm) matrix up to 10 volume percent. Three deuterated polystyrenes (dPS; M=800, 1800 and 3200 kg/mol) are chosen because their diffusion relative to NR allows for investigating fixed and mobile NR by simply changing M. For all M, the reduced tracer diffusivities are observed to decrease monotonically as NR loading increases. However, the reduced diffusivity of dPS (3200 kg/mol) is faster than expected compared to the fixed NR case. These findings suggest that mobile NR do not effectively slow down tracer diffusion relative to fixed particles. To test this hypothesis, dPS diffusion is investigated in a high molecular weight matrix PS (2000 kg/mol) in order to slow down NR diffusion relative to dPS (3200 kg/mol). New models are needed to incorporate these mobility dependent entanglements into a comprehensive understanding of dynamics in PNCs. Primary fundings: NSF/EPSRC Materials World Network DMR-1210379 (KIW, RJC) and EP/5065373/1 (NC). Support also by the NSF/MRSEC-DMR 11-20901, and Polymer Programs DMR 09-07493.

  6. Coastal Modeling System Advanced Topics

    Science.gov (United States)

    2012-06-18

    22 June 2012 - Day 5  Debugging and Problem solving  Model Calibration  Post-processing Coastal and Hydraulics Laboratory Focus of...Efficiently: • The setup process is fast and without wasted time or effort 3 Coastal and Hydraulics Laboratory 4 Coastal Modeling System (CMS) What...is the CMS? Integrated wave, current, and morphology change model in the Surface- water Modeling System (SMS). Why CMS? Operational at 10

  7. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. The overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  8. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  9. Experimental models of communication at the molecular and microsystemic levels.

    Science.gov (United States)

    Fox, S. W.; Hsu, L.; Brooke, S.; Nakashima, T.; Lacey, J. C., Jr.

    1972-01-01

    Communication at both the macromolecular and the (supramacromolecular) microsystemic levels has been demonstrated in artificial polymers and artificial systems. These phenomena are models for communication in evolving and contemporary systems. The significance of a combination of communication at the two levels is emphasized.

  10. Long-wavelength macromolecular crystallography - First successful native SAD experiment close to the sulfur edge

    Science.gov (United States)

    Aurelius, O.; Duman, R.; El Omari, K.; Mykhaylyk, V.; Wagner, A.

    2017-11-01

    Phasing of novel macromolecular crystal structures has been challenging since the start of structural biology. Making use of anomalous diffraction of natively present elements, such as sulfur and phosphorus, for phasing has been possible for some systems, but hindered by the necessity to access longer X-ray wavelengths in order to make most use of the anomalous scattering contributions of these elements. Presented here are the results from a first successful experimental phasing study of a macromolecular crystal structure at a wavelength close to the sulfur K edge. This has been made possible by the in-vacuum setup and the long-wavelength optimised experimental setup at the I23 beamline at Diamond Light Source. In these early commissioning experiments only standard data collection and processing procedures have been applied, in particular no dedicated absorption correction has been used. Nevertheless the success of the experiment demonstrates that the capability to extract phase information can be even further improved once data collection protocols and data processing have been optimised.

  11. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins has been

  12. Thermodynamic signatures in macromolecular interactions involving conformational flexibility.

    Science.gov (United States)

    Menzel, Anja; Neumann, Piotr; Schwieger, Christian; Stubbs, Milton T

    2014-07-01

    The energetics of macromolecular interactions are complex, particularly where protein flexibility is involved. Exploiting serendipitous differences in the plasticity of a series of closely related trypsin variants, we analyzed the enthalpic and entropic contributions accompanying interaction with L45K-eglin C. Binding of the four variants show significant differences in released heat, although the affinities vary little, in accordance with the principle of enthalpy-entropy compensation. Binding of the most disordered variant is almost entirely enthalpically driven, with practically no entropy change. As structures of the complexes reveal negligible differences in protein-inhibitor contacts, we conclude that solvent effects contribute significantly to binding affinities.

  13. Structural analysis of nanoparticulate carriers for encapsulation of macromolecular drugs

    Czech Academy of Sciences Publication Activity Database

    Angelov, Borislav; Garamus, V.M.; Drechsler, M.; Angelova, A.

    2017-01-01

    Roč. 235, Jun (2017), s. 83-89 ISSN 0167-7322 R&D Projects: GA MŠk EF15_003/0000447; GA MŠk EF15_008/0000162 Grant - others:OP VVV - ELIBIO(XE) CZ.02.1.01/0.0/0.0/15_003/0000447; ELI Beamlines(XE) CZ.02.1.01/0.0/0.0/15_008/0000162 Institutional support: RVO:68378271 Keywords : self-assembled nanocarriers * liquid crystalline phase transitions * cationic lipids * macromolecular drugs Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.648, year: 2016

  14. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2007-01-01

    All phenomena in nature are characterized by motion; this is an essential property of matter, having infinitely many aspects. Motion can be mechanical, physical, chemical or biological, leading to various sciences of nature, mechanics being one of them. Mechanics deals with the objective laws of mechanical motion of bodies, the simplest form of motion. In the study of a science of nature mathematics plays an important role. Mechanics is the first science of nature which was expressed in terms of mathematics by considering various mathematical models, associated to phenomena of the surrounding nature. Thus, its development was influenced by the use of a strong mathematical tool; on the other hand, we must observe that mechanics also influenced the introduction and the development of many mathematical notions. In this respect, the guideline of the present book is precisely the mathematical model of mechanics. A special accent is put on the solving methodology as well as on the mathematical tools used; vectors, ...

  15. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    In this thesis dynamic models of typical components in Danish heating systems are considered. Emphasis is made on describing and evaluating mathematical methods for identification of such models, and on presentation of component models for practical applications. The thesis consists of seven...... of component models, such as e.g. heat exchanger and valve models, adequate for system simulations. Furthermore, the thesis demonstrates and discusses the advantages and disadvantages of using statistical methods in conjunction with physical knowledge in establishing adequate component models of heating...... research papers (case studies) together with a summary report. Each case study takes it's starting point in typical heating system components and both, the applied mathematical modelling methods and the application aspects, are considered. The summary report gives an introduction to the scope...

  16. A Test of Macromolecular Crystallization in Microgravity: Large, Well-Ordered Insulin Crystals

    Science.gov (United States)

    Borgstahl, Gloria E. O.; Vahedi-Faridi, Ardeschir; Lovelace, Jeff; Bellamy, Henry D.; Snell, Edward H.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Crystals of insulin grown in microgravity on space shuttle mission STS-95 were extremely well-ordered and unusually large (many > 2 mm). The physical characteristics of six microgravity and six earth-grown crystals were examined by X-ray analysis employing superfine f slicing and unfocused synchrotron radiation. This experimental setup allowed hundreds of reflections to be precisely examined for each crystal in a short period of time. The microgravity crystals were on average 34 times larger, had 7 times lower mosaicity, had 54 times higher reflection peak heights and diffracted to significantly higher resolution than their earth grown counterparts. A single mosaic domain model could account for reflections in microgravity crystals whereas reflections from earth crystals required a model with multiple mosaic domains. This statistically significant and unbiased characterization indicates that the microgravity environment was useful for the improvement of crystal growth and resultant diffraction quality in insulin crystals and may be similarly useful for macromolecular crystals in general.

  17. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    for model reduction of switched systems is based on the switching generalized gramians. The reduced order switched system is guaranteed to be stable for all switching signal in this method. This framework uses stability conditions which are based on switching quadratic Lyapunov functions which are less...... conservative than the stability conditions based on common quadratic Lyapunov functions. The stability conditions which are used for this method are very useful in model reduction and design problems because they have slack variables in the conditions. Similar conditions for a class of switched nonlinear......High-Technological solutions of today are characterized by complex dynamical models. A lot of these models have inherent hybrid/switching structure. Hybrid/switched systems are powerful models for distributed embedded systems design where discrete controls are applied to continuous processes...

  18. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  19. Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

    Directory of Open Access Journals (Sweden)

    Hisataka Kobayashi

    2003-01-01

    Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

  20. Branched Macromolecular Architectures for Degradable, Multifunctional Phosphorus-Based Polymers.

    Science.gov (United States)

    Henke, Helena; Brüggemann, Oliver; Teasdale, Ian

    2017-02-01

    This feature article briefly highlights some of the recent advances in polymers in which phosphorus is an integral part of the backbone, with a focus on the preparation of functional, highly branched, soluble polymers. A comparison is made between the related families of materials polyphosphazenes, phosphazene/phosphorus-based dendrimers and polyphosphoesters. The work described herein shows this to be a rich and burgeoning field, rapidly catching up with organic chemistry in terms of the macromolecular synthetic control and variety of available macromolecular architectures, whilst offering unique property combinations not available with carbon backbones, such as tunable degradation rates, high multi-valency and facile post-polymerization functionalization. As an example of their use in advanced applications, we highlight some investigations into their use as water-soluble drug carriers, whereby in particular the degradability in combination with multivalent nature has made them useful materials, as underlined by some of the recent studies in this area. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Variable effects of soman on macromolecular secretion by ferret trachea

    Energy Technology Data Exchange (ETDEWEB)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of {sup 35}SO{sub 4} to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10{sup {minus} 7} M. The addition of either 10{sup {minus}6} M pralidoxime (acetylcholinesterase reactivator) or 10{sup {minus}6} M atropine blocked the response to 10{sup {minus}7} M soman. At soman concentrations greater than 10{sup {minus}7} M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors.

  2. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    Science.gov (United States)

    Shoda, Shin-ichiro; Uyama, Hiroshi; Kadokawa, Jun-ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society.

  3. Changes in the macromolecular structure of coals with pyrolysis temperature

    Energy Technology Data Exchange (ETDEWEB)

    Ndaji, F.E.; Butterfield, I.M.; Thomas, K.M. [University of Newcastle upon Tyne, Newcastle upon Tyne (United Kingdom). Northern Carbon Research Labs., Dept. of Chemistry

    1997-01-01

    The macromolecular structure of coal is characterised by its cross-link density. This paper describes a study of the effect of pyrolysis temperature on the macromolecular structure of coal using solvent swelling techniques. Heat treatment initially dissociates the intermolecular interactions in the coal and cleaves some cross-links, leading to increase in the solvent swelling of the coal, which indicates a decrease in the cross-link density. The solvent swelling reaches a maximum before cross-linking reactions predominate, causing a progressive increase in cross-link density and a decrease in solvent swelling. For lower-rank coals there appears to be an overlap (near the temperature of minimum cross-link density) of the dissociation of intermolecular interactions and thermal decomposition. Appreciable decrease in the apparent cross-link density of high-rank coals as indicated by increase in solvent swelling was observed only after thermal decomposition had commenced. Major decomposition involves cross-linking reactions leading to the formation of chars. However, the solvent swelling characteristics continue to change above the resolidification temperature, eventually ceasing at {approximately}600{degree}C. The results are discussed in relation to measurements of thermoplastic properties and devolatilization characteristics. 23 refs., 4 figs., 3 tabs.

  4. Variable effects of soman on macromolecular secretion by ferret trachea

    International Nuclear Information System (INIS)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G.

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of 35 SO 4 to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10 - 7 M. The addition of either 10 -6 M pralidoxime (acetylcholinesterase reactivator) or 10 -6 M atropine blocked the response to 10 -7 M soman. At soman concentrations greater than 10 -7 M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors

  5. PRIGo: a new multi-axis goniometer for macromolecular crystallography.

    Science.gov (United States)

    Waltersperger, Sandro; Olieric, Vincent; Pradervand, Claude; Glettig, Wayne; Salathe, Marco; Fuchs, Martin R; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias; Schulze-Briese, Clemens; Wang, Meitian

    2015-07-01

    The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0-90°), followed by a ϕ stage (0-360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  6. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2001-01-01

    For decades, distribution engineers did not have the sophisticated tools developed for analyzing transmission systems-often they had only their instincts. Things have changed, and we now have computer programs that allow engineers to simulate, analyze, and optimize distribution systems. Powerful as these programs are, however, without a real understanding of the operating characteristics of a distribution system, engineers using the programs can easily make serious errors in their designs and operating procedures. Distribution System Modeling and Analysis helps prevent those errors. It gives readers a basic understanding of the modeling and operating characteristics of the major components of a distribution system. One by one, the author develops and analyzes each component as a stand-alone element, then puts them all together to analyze a distribution system comprising the various shunt and series devices for power-flow and short-circuit studies. He includes the derivation of all models and includes many num...

  7. Hydronic distribution system computer model

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.W.; Strasser, J.J.

    1994-10-01

    A computer model of a hot-water boiler and its associated hydronic thermal distribution loop has been developed at Brookhaven National Laboratory (BNL). It is intended to be incorporated as a submodel in a comprehensive model of residential-scale thermal distribution systems developed at Lawrence Berkeley. This will give the combined model the capability of modeling forced-air and hydronic distribution systems in the same house using the same supporting software. This report describes the development of the BNL hydronics model, initial results and internal consistency checks, and its intended relationship to the LBL model. A method of interacting with the LBL model that does not require physical integration of the two codes is described. This will provide capability now, with reduced up-front cost, as long as the number of runs required is not large.

  8. Direct incorporation of prior phase information in macromolecular model refinement

    NARCIS (Netherlands)

    Skubák, Pavol

    2008-01-01

    In order to understand the function of a protein on a molecular level, the three-dimensional structure of the protein is often essential. X-ray crystallography is the primary method of protein structure determination. Despite recent rapid improvements in the field, the process of de novo structure

  9. Method for removing atomic-model bias in macromolecular crystallography

    Science.gov (United States)

    Terwilliger, Thomas C [Santa Fe, NM

    2006-08-01

    Structure factor bias in an electron density map for an unknown crystallographic structure is minimized by using information in a first electron density map to elicit expected structure factor information. Observed structure factor amplitudes are combined with a starting set of crystallographic phases to form a first set of structure factors. A first electron density map is then derived and features of the first electron density map are identified to obtain expected distributions of electron density. Crystallographic phase probability distributions are established for possible crystallographic phases of reflection k, and the process is repeated as k is indexed through all of the plurality of reflections. An updated electron density map is derived from the crystallographic phase probability distributions for each one of the reflections. The entire process is then iterated to obtain a final set of crystallographic phases with minimum bias from known electron density maps.

  10. Intrusion detection: systems and models

    Science.gov (United States)

    Sherif, J. S.; Dearmond, T. G.

    2002-01-01

    This paper puts forward a review of state of the art and state of the applicability of intrusion detection systems, and models. The paper also presents a classfication of literature pertaining to intrusion detection.

  11. Plant and safety system model

    International Nuclear Information System (INIS)

    Beltracchi, Leo

    1999-01-01

    The design and development of a digital computer-based safety system for a nuclear power plant is a complex process. The process of design and product development must result in a final product free of critical errors; operational safety of nuclear power plants must not be compromised. This paper focuses on the development of a safety system model to assist designers, developers, and regulators in establishing and evaluating requirements for a digital computer-based safety system. The model addresses hardware, software, and human elements for use in the requirements definition process. The purpose of the safety system model is to assist and serve as a guide to humans in the cognitive reasoning process of establishing requirements. The goals in the use of the model are to: (1) enhance the completeness of the requirements and (2) reduce the number of errors associated with the requirements definition phase of a project

  12. Stability of model recycled mixed plastic waste compatibilised with a cooperative compatibilisation system

    Czech Academy of Sciences Publication Activity Database

    Luzuriaga, S. E.; Kovářová, Jana; Fortelný, Ivan

    2011-01-01

    Roč. 96, č. 5 (2011), s. 751-755 ISSN 0141-3910 R&D Projects: GA MŠk 2B06097 Institutional research plan: CEZ:AV0Z40500505 Keywords : polymer recycling * reactive compatibilisation system * stabilization Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.769, year: 2011

  13. Mathematical modeling of aeroelastic systems

    Science.gov (United States)

    Velmisov, Petr A.; Ankilov, Andrey V.; Semenova, Elizaveta P.

    2017-12-01

    In the paper, the stability of elastic elements of a class of designs that are in interaction with a gas or liquid flow is investigated. The definition of the stability of an elastic body corresponds to the concept of stability of dynamical systems by Lyapunov. As examples the mathematical models of flowing channels (models of vibration devices) at a subsonic flow and the mathematical models of protective surface at a supersonic flow are considered. Models are described by the related systems of the partial differential equations. An analytic investigation of stability is carried out on the basis of the construction of Lyapunov-type functionals, a numerical investigation is carried out on the basis of the Galerkin method. The various models of the gas-liquid environment (compressed, incompressible) and the various models of a deformable body (elastic linear and elastic nonlinear) are considered.

  14. ABSTRACT MODELS FOR SYSTEM VIRTUALIZATION

    Directory of Open Access Journals (Sweden)

    M. G. Koveshnikov

    2015-05-01

    Full Text Available The paper is dedicated to issues of system objects securing (system files and user system or application configuration files against unauthorized access including denial of service attacks. We have suggested the method and developed abstract system virtualization models, which are used toresearch attack scenarios for different virtualization modes. Estimation for system tools virtualization technology effectiveness is given. Suggested technology is based on redirection of access requests to system objects shared among access subjects. Whole and partial system virtualization modes have been modeled. The difference between them is the following: in the whole virtualization mode all copies of access system objects are created whereon subjects’ requests are redirected including corresponding application objects;in the partial virtualization mode corresponding copies are created only for part of a system, for example, only system objects for applications. Alternative solutions effectiveness is valued relating to different attack scenarios. We consider proprietary and approved technical solution which implements system virtualization method for Microsoft Windows OS family. Administrative simplicity and capabilities of correspondingly designed system objects security tools are illustrated on this example. Practical significance of the suggested security method has been confirmed.

  15. Aerodynamic and Mechanical System Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix

    This thesis deals with mechanical multibody-systems applied to the drivetrain of a 500 kW wind turbine. Particular focus has been on gearbox modelling of wind turbines. The main part of the present project involved programming multibody systems to investigate the connection between forces, moments...

  16. OCTOPUS: an innovative multimodal diffractometer for neutron macromolecular crystallography across the length scales

    International Nuclear Information System (INIS)

    Blakeley, M.P.; Andersen, K.; Kreuz, M.; Giroud, B.; McSweeney, S.; Mitchell, E.; Teixeira, S.C.M.; Forsyth, V.T.

    2011-01-01

    We propose to construct a novel protein diffractometer at position H112B. The new instrument will deliver major efficiency gains, as well as offering greatly extended flexibility through the option of several easily interchangeable modes of operation. This proposal builds on the demonstrable need to extend ILL's capacity for high resolution structural studies of protein systems, as well as a need to widen the scope of biological crystallography - in particular for monochromatic studies at both high and low resolution. The development will be carried out in close collaboration with structural biologists at the ESRF, and engineered in such a way that the user interface of the instrument (from sample to software) will be transparently identifiable to a large, dynamic, and driven community of European synchrotron X-ray macromolecular crystallographers. (authors)

  17. A vibrating membrane bioreactor (VMBR): Macromolecular transmission-influence of extracellular polymeric substances

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2009-01-01

    The vibrating membrane bioreactor (VMBR) system facilitates the possibility of conducting a separation of macromolecules (BSA) from larger biological components (yeast cells) with a relatively high and stable macromolecular transmission at sub-critical flux. This is not possible to achieve...... for a static non-vibrating membrane module. A BSA transmission of 74% has been measured in the separation of 4g/L BSA from 8 g/L dry weight yeast cells in suspension at sub-critical flux (20L/(m(2) h)). However, this transmission is lower than the 85% BSA transmission measured for at pure 4g/L BSA solution...... of around 32% is measured for a pure yeast cell suspension. Thus, EPS and BSA are "competing" in being transmitted which might explain the lowered BSA transmission in the presence of yeast cells. Additionally, EPS heavily foul the membranes, leading to a 86% permeability drop and a fouling resistance 6...

  18. Automated Protocols for Macromolecular Crystallization at the MRC Laboratory of Molecular Biology.

    Science.gov (United States)

    Gorrec, Fabrice; Löwe, Jan

    2018-01-24

    When high quality crystals are obtained that diffract X-rays, the crystal structure may be solved at near atomic resolution. The conditions to crystallize proteins, DNAs, RNAs, and their complexes can however not be predicted. Employing a broad variety of conditions is a way to increase the yield of quality diffraction crystals. Two fully automated systems have been developed at the MRC Laboratory of Molecular Biology (Cambridge, England, MRC-LMB) that facilitate crystallization screening against 1,920 initial conditions by vapor diffusion in nanoliter droplets. Semi-automated protocols have also been developed to optimize conditions by changing the concentrations of reagents, the pH, or by introducing additives that potentially enhance properties of the resulting crystals. All the corresponding protocols will be described in detail and briefly discussed. Taken together, they enable convenient and highly efficient macromolecular crystallization in a multi-user facility, while giving the users control over key parameters of their experiments.

  19. Preface: the hydra model system.

    Science.gov (United States)

    Galliot, Brigitte

    2012-01-01

    The freshwater Hydra polyp emerged as a model system in 1741 when Abraham Trembley not only discovered its amazing regenerative potential, but also demonstrated that experimental manipulations pave the way to research in biology. Since then, Hydra flourished as a potent and fruitful model system to help answer questions linked to cell and developmental biology, as such as the setting up of an organizer to regenerate a complex missing structure, the establishment and maintainance of polarity in a multicellular organism, the development of mathematical models to explain the robust developmental rules observed in this animal, the maintainance of stemness and multipotency in a highly dynamic environment, the plasticity of differentiated cells, to name but a few. However the Hydra model system is not restricted to cell and developmental biology; during the past 270 years it has also been heavily used to investigate the relationships between Hydra and its environment, opening new horizons concerning neurophysiology, innate immunity, ecosystems, ecotoxicology, symbiosis...

  20. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  1. System Convergence in Transport Modelling

    DEFF Research Database (Denmark)

    Rich, Jeppe; Nielsen, Otto Anker; Cantarella, Guilio E.

    2010-01-01

    A fundamental premise of most applied transport models is the existence and uniqueness of an equilibrium solution that balances demand x(t) and supply t(x). The demand consists of the people that travel in the transport system and on the defined network, whereas the supply consists of the resulting...... level-of-service attributes (e.g., travel time and cost) offered to travellers. An important source of complexity is the congestion, which causes increasing demand to affect travel time in a non-linear way. Transport models most often involve separate models for traffic assignment and demand modelling...

  2. NATO Advanced Study Institute on Evolving Methods for Macromolecular Gystallography

    CERN Document Server

    Read, Randy J

    2007-01-01

    X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes, and to discovering novel therapeutics using a structure-based approach. As yet, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown. This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis, and show how modern high-throughput methods are contributing to a deeper understanding of medical problems.

  3. In-vacuum long-wavelength macromolecular crystallography.

    Science.gov (United States)

    Wagner, Armin; Duman, Ramona; Henderson, Keith; Mykhaylyk, Vitaliy

    2016-03-01

    Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

  4. Comparative and evolutionary aspects of macromolecular translocation across membranes.

    Science.gov (United States)

    Tartakoff, Alan M; Tao, Tao

    2010-02-01

    Membrane barriers preserve the integrity of organelles of eukaryotic cells, yet the genesis and ongoing functions of the same organelles requires that their limiting membranes allow import and export of selected macromolecules. Multiple distinct mechanisms are used for this purpose, only some of which have been traced to prokaryotes. Some can accommodate both monomeric and also large heterooligomeric cargoes. The best characterized of these is nucleocytoplasmic transport. This synthesis compares the unidirectional and bidirectional mechanisms of macromolecular transport of the endoplasmic reticulum, mitochondria, peroxisomes and the nucleus, calls attention to the powerful experimental approaches which have been used for their elucidation, discusses their regulation and evolutionary origins, and highlights relatively unexplored areas. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  5. Large-volume protein crystal growth for neutron macromolecular crystallography.

    Science.gov (United States)

    Ng, Joseph D; Baird, James K; Coates, Leighton; Garcia-Ruiz, Juan M; Hodge, Teresa A; Huang, Sijay

    2015-04-01

    Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.

  6. Designing a synchrotron micro-focusing beamline for macromolecular crystallography.

    Science.gov (United States)

    Grochulski, Paweł; Cygler, Mirosław; Yates, Brian

    After a successful 10 years of operation, the Canadian Macromolecular Crystallography Facility 08ID-1 beamline will undergo an upgrade to establish micro-beam capability. This paper is mostly focussed on optics and computer simulations for ray tracing of the beamline. After completion, the focussed beam at the sample will have a much smaller size of 50 × 5 µm 2 (H x V), allowing measurement of X-ray diffraction patterns from much smaller crystals than possible presently. The beamline will be equipped with a fast sample changer and an ultra-low noise photon counting detector, allowing shutter-less operation of the beamline. Additionally, it will be possible to perform in-situ room-temperature experiments.

  7. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  8. Single-particle cryo-electron microscopy of macromolecular complexes.

    Science.gov (United States)

    Skiniotis, Georgios; Southworth, Daniel R

    2016-02-01

    Recent technological breakthroughs in image acquisition have enabled single-particle cryo-electron microscopy (cryo-EM) to achieve near-atomic resolution structural information for biological complexes. The improvements in image quality coupled with powerful computational methods for sorting distinct particle populations now also allow the determination of compositional and conformational ensembles, thereby providing key insights into macromolecular function. However, the inherent instability and dynamic nature of biological assemblies remain a tremendous challenge that often requires tailored approaches for successful implementation of the methodology. Here, we briefly describe the fundamentals of single-particle cryo-EM with an emphasis on covering the breadth of techniques and approaches, including low- and high-resolution methods, aiming to illustrate specific steps that are crucial for obtaining structural information by this method. © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Balanced macromolecular biosynthesis in "protoplasts" of Streptococcus faecalis.

    Science.gov (United States)

    Roth, G S; Shockman, G D; Daneo-Moore, L

    1971-03-01

    Osmotically fragile forms of Streptococcus faecalis 9790 were grown in 0.5 m sucrose- or 0.5 m NH(4)Cl-stabilized medium. The "protoplast" cultures exhibit an average growth rate constant of 0.66 to 0.94 mass doublings/hr. In a variety of experiments, turbidity and the net content of protein, ribonucleic acid (RNA) and deoxyribonucleic acid increase at the same rate, indicating balanced macromolecular biosynthesis. A total of two to three mass doublings was obtained, with no evidence of cell division. After osmotic shock, "protoplast" cultures released 93 to 94% of their RNA content in a form not sedimentable at 12,800 x g for 15 min, in contrast to streptococci, which released 7% of their RNA content after the same treatment.

  10. 129 Xe NMR Relaxation-Based Macromolecular Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Muller D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Dao, Phuong [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Jeong, Keunhong [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Slack, Clancy C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Vassiliou, Christophoros C. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Finbloom, Joel A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Francis, Matthew B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Wemmer, David E. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; Pines, Alexander [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    2016-07-29

    A 129Xe NMR relaxation-based sensing approach is reported on that exploits changes in the bulk xenon relaxation rate induced by slowed tumbling of a cryptophane-based sensor upon target binding. The amplification afforded by detection of the bulk dissolved xenon allows sensitive detection of targets. The sensor comprises a xenon-binding cryptophane cage, a target interaction element, and a metal chelating agent. Xenon associated with the target-bound cryptophane cage is rapidly relaxed and then detected after exchange with the bulk. Here we show that large macromolecular targets increase the rotational correlation time of xenon, increasing its relaxation rate. Upon binding of a biotin-containing sensor to avidin at 1.5 μM concentration, the free xenon T2 is reduced by a factor of 4.

  11. E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

    Science.gov (United States)

    Boutselakis, H; Dimitropoulos, D; Fillon, J; Golovin, A; Henrick, K; Hussain, A; Ionides, J; John, M; Keller, P A; Krissinel, E; McNeil, P; Naim, A; Newman, R; Oldfield, T; Pineda, J; Rachedi, A; Copeland, J; Sitnov, A; Sobhany, S; Suarez-Uruena, A; Swaminathan, J; Tagari, M; Tate, J; Tromm, S; Velankar, S; Vranken, W

    2003-01-01

    The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

  12. Cryo-electron Microscopy Analysis of Structurally Heterogeneous Macromolecular Complexes.

    Science.gov (United States)

    Jonić, Slavica

    2016-01-01

    Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e.g., membrane proteins) whose size was earlier an obstacle to cryo-EM. Image analysis to identify multiple coexisting structures in the same specimen (multiconformation reconstruction) is now routinely done both to solve structures at near-atomic resolution and to study conformational dynamics. Methods for multiconformation reconstruction and latest examples of their applications are the focus of this review.

  13. Extracting trends from two decades of microgravity macromolecular crystallization history.

    Science.gov (United States)

    Judge, Russell A; Snell, Edward H; van der Woerd, Mark J

    2005-06-01

    Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

  14. Macromolecular structure analysis and effective liquefaction pretreatment. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Suuberg, E.M.; Yun, Y.; Lilly, W.D.; Leung, K.; Gates, T.; Otake, Y.; Deevi, S.C.

    1994-07-01

    This project was concerned with characterizing the changes in coal macromolecular structure, that are of significance for liquefaction pretreatments of coal. The macromolecular structure of the insoluble portion of coal is difficult to characterize. Techniques that do so indirectly (based upon, for example, NMR and FTIR characterizations of atomic linkages) are not particularly sensitive for this purpose. Techniques that characterize the elastic structure (such as solvent swelling) are much more sensitive to subtle changes in the network structure. It is for this reason that we focused upon these techniques. The overall objective involved identifying pretreatments that reduce the crosslinking (physical or chemical) of the network structure, and thus lead to materials that can be handled to a greater extent by traditional liquid-phase processing techniques. These techniques tend to be inherently more efficient at producing desirable products. This report is divided into seven chapters. Chapter II summarizes the main experimental approaches used throughout the project, and summarizes the main findings on the Argonne Premium coal samples. Chapter III considers synergistic effects of solvent pairs. It is divided into two subsections. The first is concerned with mixtures of CS{sub 2} with electron donor solvents. The second subsection is concerned with aromatic hydrocarbon - alcohol or hydrocarbon - alcohol mixtures, as might be of interest for preliquefaction delivery of catalysts into bituminous coals. Chapter IV deals with questions of how oxidation might influence the results that are obtained. Chapter V briefly details what conclusions may be drawn concerning the elastic behavior of coals, and the effects of thermal treatments on this behavior. Chapter VI is concerned with theories to describe the action of solvents that are capable of dissociating non-covalent crosslinks. Finally, Chapter VII discusses the practical implications of the study.

  15. Executive Information Systems' Multidimensional Models

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

  16. Macromolecular Stabilization by Excluded Cosolutes: Mean Field Theory of Crowded Solutions.

    Science.gov (United States)

    Sapir, Liel; Harries, Daniel

    2015-07-14

    We propose a mean field theory to account for the experimentally determined temperature dependence of protein stabilization that emerges in solutions crowded by preferentially excluded cosolutes. Based on regular solution theory and employing the Flory-Huggins approximation, our model describes cosolutes in terms of their size, and two temperature-dependent microscopic parameters that correspond to macromolecule-cosolute and bulk solution interactions. The theory not only predicts a "depletion force" that can account for the experimentally observed stabilization of protein folding or association in the presence of excluded cosolutes but also predicts the full range of associated entropic and enthalpic components. Remarkably, depending on cosolute identity and in accordance with experiments, the theory describes entropically as well as enthalpically dominated depletion forces, even those disfavored by entropy. This emerging depletion attraction cannot be simply linked to molecular volumes. Instead, the relevant parameter is an effective volume that represents an interplay between solvent, cosolute, and macromolecular interactions. We demonstrate that the apparent depletion free energy is often accompanied by significant yet compensating entropy and enthalpy terms that, although having a net zero contribution to stabilization, can obscure the underlying molecular mechanism. This study underscores the importance of including often-neglected free energy terms that correspond to solvent-cosolute and cosolute-macromolecule interactions, which for most typical cosolutes are expected to be temperature dependent. We propose that experiments specifically aimed at resolving the temperature-dependence of cosolute exclusion from macromolecular surfaces should help reveal the full range of the underlying molecular mechanisms of the depletion force.

  17. Numerical Modeling of Microelectrochemical Systems

    DEFF Research Database (Denmark)

    Adesokan, Bolaji James

    for the reactants in the bulk electrolyte that are traveling waves. The first paper presents the mathematical model which describes an electrochemical system and simulates an electroanalytical technique called cyclic voltammetry. The model is governed by a system of advection–diffusion equations with a nonlinear...... reaction term at the boundary. We investigate the effect of flow rates, scan rates, and concentration on the cyclic voltammetry. We establish that high flow rates lead to the reduced hysteresis in the cyclic voltammetry curves and increasing scan rates lead to more pronounced current peaks. The final part...... of the paper shows that the response current in a cyclic voltammetry increases proportionally to the electrolyte concentration. In the second paper we present an experiment of an electrochemical system in a microfluidc system and compare the result to the numerical solutions. We investigate how the position...

  18. System Code Models and Capabilities

    International Nuclear Information System (INIS)

    Bestion, D.

    2008-01-01

    System thermalhydraulic codes such as RELAP, TRACE, CATHARE or ATHLET are now commonly used for reactor transient simulations. The whole methodology of code development is described including the derivation of the system of equations, the analysis of experimental data to obtain closure relation and the validation process. The characteristics of the models are briefly presented starting with the basic assumptions, the system of equations and the derivation of closure relationships. An extensive work was devoted during the last three decades to the improvement and validation of these models, which resulted in some homogenisation of the different codes although separately developed. The so called two-fluid model is the common basis of these codes and it is shown how it can describe both thermal and mechanical nonequilibrium. A review of some important physical models allows to illustrate the main capabilities and limitations of system codes. Attention is drawn on the role of flow regime maps, on the various methods for developing closure laws, on the role of interfacial area and turbulence on interfacial and wall transfers. More details are given for interfacial friction laws and their relation with drift flux models. Prediction of chocked flow and CFFL is also addressed. Based on some limitations of the present generation of codes, perspectives for future are drawn.

  19. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...... insight. It is based on a sensitivity approach that is useful for choice of model structure, for experiment design, and for accuracy verification. The method is implemented in the Matlab toolkit Senstools. The method and the presentation have been developed with generally preferred learning styles in mind...

  20. Development of an online UV–visible microspectrophotometer for a macromolecular crystallography beamline

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Nobutaka, E-mail: nobutaka.shimizu@kek.jp [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Shimizu, Tetsuya [RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Baba, Seiki; Hasegawa, Kazuya [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Yamamoto, Masaki [RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Kumasaka, Takashi [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan)

    2013-11-01

    An online UV–visible microspectrophotometer has been developed for the macromolecular crystallography beamline at SPring-8. Details of this spectrophotometer are reported. Measurement of the UV–visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV–visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury–xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

  1. Compositional Modeling of Biological Systems

    OpenAIRE

    Zámborszky, Judit

    2010-01-01

    Molecular interactions are wired in a fascinating way resulting in complex behavior of bio-logical systems. Theoretical modeling provides us a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological systems calls for conceptual tools that manage the combinatorial explosion of the set of possible interac-tions. A suitable conceptual tool to attack complexity is compositionality, already success-fully used in the process algebra field ...

  2. Effect of the hardener to epoxy monomer ratio on the water absorption behavior of the DGEBA/TETA epoxy system

    Directory of Open Access Journals (Sweden)

    Ayrton Alef Castanheira Pereira

    2016-02-01

    Full Text Available Abstract The water absorption behavior of the DGEBA/TETA epoxy system was evaluated as a function of the epoxy monomer to amine hardener ratio. Weight gain versus immersion time curves were obtained and the experimental points were fitted using Fickian and Non-Fickian diffusion models. The results obtained showed that for all epoxy monomer to hardener ratios analyzed water diffusion followed non-Fickian behavior. It was possible to correlate the water absorption behavior to the macromolecular structure developed when the epoxy/ hardener ratio was varied. All epoxy/hardener ratios present a two-phase macromolecular structure, composed of regions with high crosslink density and regions with lower crosslinking. Epoxy rich systems have a more open macromolecular structure with a lower fraction of the dense phase than the amine rich systems, which present a more compact two-phase structure.

  3. Parametric Modeling for Fluid Systems

    Science.gov (United States)

    Pizarro, Yaritzmar Rosario; Martinez, Jonathan

    2013-01-01

    Fluid Systems involves different projects that require parametric modeling, which is a model that maintains consistent relationships between elements as is manipulated. One of these projects is the Neo Liquid Propellant Testbed, which is part of Rocket U. As part of Rocket U (Rocket University), engineers at NASA's Kennedy Space Center in Florida have the opportunity to develop critical flight skills as they design, build and launch high-powered rockets. To build the Neo testbed; hardware from the Space Shuttle Program was repurposed. Modeling for Neo, included: fittings, valves, frames and tubing, between others. These models help in the review process, to make sure regulations are being followed. Another fluid systems project that required modeling is Plant Habitat's TCUI test project. Plant Habitat is a plan to develop a large growth chamber to learn the effects of long-duration microgravity exposure to plants in space. Work for this project included the design and modeling of a duct vent for flow test. Parametric Modeling for these projects was done using Creo Parametric 2.0.

  4. Integrative structure modeling with the Integrative Modeling Platform.

    Science.gov (United States)

    Webb, Benjamin; Viswanath, Shruthi; Bonomi, Massimiliano; Pellarin, Riccardo; Greenberg, Charles H; Saltzberg, Daniel; Sali, Andrej

    2018-01-01

    Building models of a biological system that are consistent with the myriad data available is one of the key challenges in biology. Modeling the structure and dynamics of macromolecular assemblies, for example, can give insights into how biological systems work, evolved, might be controlled, and even designed. Integrative structure modeling casts the building of structural models as a computational optimization problem, for which information about the assembly is encoded into a scoring function that evaluates candidate models. Here, we describe our open source software suite for integrative structure modeling, Integrative Modeling Platform (https://integrativemodeling.org), and demonstrate its use. © 2017 The Protein Society.

  5. Model checking embedded system designs

    NARCIS (Netherlands)

    Brinksma, Hendrik; Mader, Angelika H.

    2002-01-01

    Model checking has established itself as a successful tool supported technique for the verification and debugging of various hardware and software systems [16]. Not only in academia, but also by industry this technique is increasingly being regarded as a promising and practical proposition,

  6. GENERIC model for multiphase systems

    NARCIS (Netherlands)

    Sagis, L.M.C.

    2010-01-01

    GENERIC is a nonequilibrium thermodynamic formalism in which the dynamic behavior of a system is described by a single compact equation involving two types of brackets: a Poisson bracket and a dissipative bracket. This formalism has proved to be a very powerful instrument to model the dynamic

  7. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    Analysing real-world systems for vulnerabilities with respect to security and safety threats is a difficult undertaking, not least due to a lack of availability of formalisations for those systems. While both formalisations and analyses can be found for artificial systems such as software......, this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...... are based on (quite successful) ad-hoc techniques. We believe they can be significantly improved beyond the state-of-the-art by pairing them with static analyses techniques. In this paper we present an approach to both formalising those real-world systems, as well as providing an underlying semantics, which...

  8. Systems modeling for laser IFE

    Science.gov (United States)

    Meier, W. R.; Raffray, A. R.; Sviatoslavsky, I. N.

    2006-06-01

    A systems model of a laser-driven IFE power plant is being developed to assist in design trade-offs and optimization. The focus to date has been on modeling the fusion chamber, blanket and power conversion system. A self-consistent model has been developed to determine key chamber and thermal cycle parameters (e.g., chamber radius, structure and coolant temperatures, cycle efficiency, etc.) as a function of the target yield and pulse repetition rate. Temperature constraints on the tungsten armor, ferritic steel wall, and structure/coolant interface are included in evaluating the potential design space. Results are presented for a lithium cooled first wall coupled with a Brayton power cycle. LLNL work performed under the auspices of the US Department of Energy by the University of California LLNL under Contract W-7405-Eng-48.

  9. Cotangent Models for Integrable Systems

    Science.gov (United States)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

    We associate cotangent models to a neighbourhood of a Liouville torus in symplectic and Poisson manifolds focusing on b-Poisson/ b-symplectic manifolds. The semilocal equivalence with such models uses the corresponding action-angle theorems in these settings: the theorem of Liouville-Mineur-Arnold for symplectic manifolds and an action-angle theorem for regular Liouville tori in Poisson manifolds (Laurent- Gengoux et al., IntMath Res Notices IMRN 8: 1839-1869, 2011). Our models comprise regular Liouville tori of Poisson manifolds but also consider the Liouville tori on the singular locus of a b-Poisson manifold. For this latter class of Poisson structures we define a twisted cotangent model. The equivalence with this twisted cotangent model is given by an action-angle theorem recently proved by the authors and Scott (Math. Pures Appl. (9) 105(1):66-85, 2016). This viewpoint of cotangent models provides a new machinery to construct examples of integrable systems, which are especially valuable in the b-symplectic case where not many sources of examples are known. At the end of the paper we introduce non-degenerate singularities as lifted cotangent models on b-symplectic manifolds and discuss some generalizations of these models to general Poisson manifolds.

  10. Graph modeling systems and methods

    Science.gov (United States)

    Neergaard, Mike

    2015-10-13

    An apparatus and a method for vulnerability and reliability modeling are provided. The method generally includes constructing a graph model of a physical network using a computer, the graph model including a plurality of terminating vertices to represent nodes in the physical network, a plurality of edges to represent transmission paths in the physical network, and a non-terminating vertex to represent a non-nodal vulnerability along a transmission path in the physical network. The method additionally includes evaluating the vulnerability and reliability of the physical network using the constructed graph model, wherein the vulnerability and reliability evaluation includes a determination of whether each terminating and non-terminating vertex represents a critical point of failure. The method can be utilized to evaluate wide variety of networks, including power grid infrastructures, communication network topologies, and fluid distribution systems.

  11. Effects of osmolytes and macromolecular crowders on stable GAAA tetraloops and their preference for a CG closing base pair

    Directory of Open Access Journals (Sweden)

    Kaethe N. Leonard

    2018-02-01

    Full Text Available Osmolytes and macromolecular crowders have the potential to influence the stability of secondary structure motifs and alter preferences for conserved nucleic acid sequences in vivo. To further understand the cellular function of RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG 200, and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif. GAAA tetraloops are conserved, stable tetraloops, and are critical participants in RNA tertiary structure. They also have a thermodynamic preference for a CG closing base pair. The thermal denaturation of model hairpins containing GAAA loops was monitored using UV-Vis spectroscopy in the presence and absence of PEG 200 or PEG 8000. Both of the cosolutes tested influenced the thermodynamic preference for a CG base pair by destabilizing the loop with a CG closing base pair relative to the loop with a GC closing base pair. This result also extended to a related DNA triloop, which provides further evidence that the interactions between the loop and closing base pair are identical for the d(GCA triloop and the GAAA tetraloop. Our results suggest that in the presence of model PEG molecules, loops with a GC closing base pair may retain some preferential interactions with the cosolutes that are lost in the presence of the CG closing base pair. These results reveal that relatively small structural changes could influence how neutral cosolutes tune the stability and function of secondary structure motifs in vivo.

  12. Fluid Physics and Macromolecular Crystal Growth in Microgravity

    Science.gov (United States)

    Helliwell, John R.; Snell, Edward H.; Chayen, Naomi E.; Judge, Russell A.; Boggon, Titus J.; Pusey, M. L.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    The first protein crystallization experiment in microgravity was launched in April, 1981 and used Germany's Technologische Experimente unter Schwerelosigkeit (TEXUS 3) sounding rocket. The protein P-galactosidase (molecular weight 465Kda) was chosen as the sample with a liquid-liquid diffusion growth method. A sliding device brought the protein, buffer and salt solution into contact when microgravity was reached. The sounding rocket gave six minutes of microgravity time with a cine camera and schlieren optics used to monitor the experiment, a single growth cell. In microgravity a strictly laminar diffusion process was observed in contrast to the turbulent convection seen on the ground. Several single crystals, approx 100micron in length, were formed in the flight which were of inferior but of comparable visual quality to those grown on the ground over several days. A second experiment using the same protocol but with solutions cooled to -8C (kept liquid with glycerol antifreeze) again showed laminar diffusion. The science of macromolecular structural crystallography involves crystallization of the macromolecule followed by use of the crystal for X-ray diffraction experiments to determine the three dimensional structure of the macromolecule. Neutron protein crystallography is employed for elucidation of H/D exchange and for improved definition of the bound solvent (D20). The structural information enables an understanding of how the molecule functions with important potential for rational drug design, improved efficiency of industrial enzymes and agricultural chemical development. The removal of turbulent convection and sedimentation in microgravity, and the assumption that higher quality crystals will be produced, has given rise to the growing number of crystallization experiments now flown. Many experiments can be flown in a small volume with simple, largely automated, equipment - an ideal combination for a microgravity experiment. The term "protein crystal growth

  13. Probabilistic models for feedback systems.

    Energy Technology Data Exchange (ETDEWEB)

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

    In previous work, we developed a Bayesian-based methodology to analyze the reliability of hierarchical systems. The output of the procedure is a statistical distribution of the reliability, thus allowing many questions to be answered. The principal advantage of the approach is that along with an estimate of the reliability, we also can provide statements of confidence in the results. The model is quite general in that it allows general representations of all of the distributions involved, it incorporates prior knowledge into the models, it allows errors in the 'engineered' nodes of a system to be determined by the data, and leads to the ability to determine optimal testing strategies. In this report, we provide the preliminary steps necessary to extend this approach to systems with feedback. Feedback is an essential component of 'complexity' and provides interesting challenges in modeling the time-dependent action of a feedback loop. We provide a mechanism for doing this and analyze a simple case. We then consider some extensions to more interesting examples with local control affecting the entire system. Finally, a discussion of the status of the research is also included.

  14. Stochastic Modelling of Hydrologic Systems

    DEFF Research Database (Denmark)

    Jonsdottir, Harpa

    2007-01-01

    In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains an introduct......In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains...... an introduction and an overview of the papers published. Then an introduction to basic concepts in hydrology along with a description of hydrological data is given. Finally an introduction to stochastic modelling is given. The second part contains the research papers. In the research papers the stochastic methods...... are described, as at the time of publication these methods represent new contribution to hydrology. The second part also contains additional description of software used and a brief introduction to stiff systems. The system in one of the papers is stiff....

  15. Discrete modelling of drapery systems

    Science.gov (United States)

    Thoeni, Klaus; Giacomini, Anna

    2016-04-01

    Drapery systems are an efficient and cost-effective measure in preventing and controlling rockfall hazards on rock slopes. The simplest form consists of a row of ground anchors along the top of the slope connected to a horizontal support cable from which a wire mesh is suspended down the face of the slope. Such systems are generally referred to as simple or unsecured draperies (Badger and Duffy 2012). Variations such as secured draperies, where a pattern of ground anchors is incorporated within the field of the mesh, and hybrid systems, where the upper part of an unsecured drapery is elevated to intercept rockfalls originating upslope of the installation, are becoming more and more popular. This work presents a discrete element framework for simulation of unsecured drapery systems and its variations. The numerical model is based on the classical discrete element method (DEM) and implemented into the open-source framework YADE (Šmilauer et al., 2010). The model takes all relevant interactions between block, drapery and slope into account (Thoeni et al., 2014) and was calibrated and validated based on full-scale experiments (Giacomini et al., 2012).The block is modelled as a rigid clump made of spherical particles which allows any shape to be approximated. The drapery is represented by a set of spherical particle with remote interactions. The behaviour of the remote interactions is governed by the constitutive behaviour of the wire and generally corresponds to a piecewise linear stress-strain relation (Thoeni et al., 2013). The same concept is used to model wire ropes. The rock slope is represented by rigid triangular elements where material properties (e.g., normal coefficient of restitution, friction angle) are assigned to each triangle. The capabilities of the developed model to simulate drapery systems and estimate the residual hazard involved with such systems is shown. References Badger, T.C., Duffy, J.D. (2012) Drapery systems. In: Turner, A.K., Schuster R

  16. Use of non-linear properties of stimuli-sensitive polymers in image display systems

    Czech Academy of Sciences Publication Activity Database

    Suleimenov, I.; Semenyakin, N.; Mun, G.; Shaltykova, D.; Panchenko, S.; Sedláková, Zdeňka

    2012-01-01

    Roč. 3, 2012 (2012), s. 528-533 ISSN 2212-6716. [2012 Conference on Modelling, Identification and Control - MIC 2012. Hong Kong , 19.12.2012-20.12.2012] Institutional support: RVO:61389013 Keywords : display systems * stimuli-sensitive polymers * phase transition Subject RIV: CD - Macromolecular Chemistry

  17. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2015-03-01

    Full Text Available Yi Liu,1 Hongyu Piao,1 Ying Gao,1 Caihong Xu,2 Ye Tian,1 Lihong Wang,1 Jinwen Liu,1 Bo Tang,1 Meijuan Zou,1 Gang Cheng1 1Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Food Science, Shenyang Normal University, Shenyang, Liaoning Province, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN38, an active metabolite of irinotecan (CPT-11, is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OHSN38 and chitosan-(C20-OHSN38 to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OHSN38 (CS-(10sSN38 and chitosan-(C20-OHSN38 (CS-(20sSN38 were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC0–24 of SN38 after intravenously administering CS-(10sSN38 and CS-(20sSN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01. A larger AUC0–24 of CS-(20sSN38 was observed when compared to CS-(10sSN38 (P<0.05. Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20sSN38 exhibited better in vivo antitumor activity than CS-(10sSN38 at a dose of 2.5 mg/kg (P<0

  18. Use of Capillaries for Macromolecular Crystallization in a Cryogenic Dewar

    Science.gov (United States)

    Ciszak, Ewa; Hammons, Aaron S.; Hong, Young Soo

    2002-01-01

    The enhanced gaseous nitrogen (EGN) dewar is a cryogenic dry shipper with a sealed cylinder inserted inside along with a temperature monitoring device, and is intended for macromolecular crystallization experiments on the International Space Station. Within the dewar, each crystallization experiment is contained as a solution within a plastic capillary tube. The standard procedure for loading samples in these tubes has involved rapid freezing of the precipitant and biomolecular solution, e.g., protein, directly in liquid nitrogen; this method, however, often resulted in uncontrolled formation of air voids, These air pockets, or bubbles, can lead to irreproducible crystallization results. A novel protocol has been developed to prevent formation of bubbles, and this has been tested in the laboratory as well as aboard the International Space Station during a 42-day long mission of July/August 2001. The gain or loss of mass from solutions within the plastic capillaries revealed that mass transport occurred among separated tubes, and that this mass transport was dependent upon the hygroscopic character of the solution contained in any given tube. The surface area of the plastic capillary tube also related to the observed mass transport. Furthermore, the decreased mass of solutions of-protein correlated to observed formation of protein crystals.

  19. A beamline for macromolecular crystallography at the Advanced Light Source

    International Nuclear Information System (INIS)

    Padmore, H.A.; Earnest, T.; Kim, S.H.; Thompson, A.C.; Robinson, A.L.

    1994-08-01

    A beamline for macromolecular crystallography has been designed for the ALS. The source will be a 37-pole wiggler with a, 2-T on-axis peak field. The wiggler will illuminate three beamlines, each accepting 3 mrad of horizontal aperture. The central beamline will primarily be used for multiple-wavelength anomalous dispersion measurements in the wavelength range from 4 to 0.9 angstrom. The beamline optics will comprise a double-crystal monochromator with a collimating pre-mirror and a double-focusing mirror after the monochromator. The two side stations will be used for fixed-wavelength experiments within the wavelength range from 1.5 to 0.95 angstrom. The optics will consist of a conventional vertically focusing cylindrical mirror followed by an asymmetrically cut curved-crystal monochromator. This paper presents details of the optimization of the wiggler source for crystallography, gives a description of the beamline configuration, and discusses the reasons for the choices made

  20. Macromolecular Crystallography and Structural Biology Databases at NIST.

    Science.gov (United States)

    Gilliland, G L

    2001-01-01

    In the late 1970s, macromolecular crystallography at NIST began with collaboration between NIST and NIH to establish a single-crystal neutron diffractometer. This instrument was constructed and employed to solve a number of crystal structures: bovine ribonuclease A, bovine-ribonuclease-uridine vanadate complex, and porcine insulin. In the mid 1980s a Biomolecular Structure Group was created establishing NIST capabilities in biomolecular singe-crystal x-ray diffraction. The group worked on a variety of structural problems until joining the NIST/UMBI Center for Advanced Research in Biotechnology (CARB) in 1987. Crystallographic studies at CARB were then focused on protein engineering efforts that included among others chymosin, subtilisin BPN', interleukin 1β, and glutathione S-transferase. Recently, the structural biology efforts have centered on enzymes in the chorismate metabolic pathways involved in amino acid biosynthesis and in structural genomics that involves determining the structures of "hypothetical" proteins to aid in assigning function. In addition to crystallographic studies, structural biology database activities began with the formal establishment of the Biological Macro-molecule Crystallization Database in 1989. Later, in 1997, NIST in partnership with Rutgers and UCSD formed the Research Collaboratory for Structural Bioinformatics that successfully acquired the Protein Data Bank. The NIST efforts in these activities have focused on data uniformity, establishing and maintaining the physical archive, and working with the NMR community.

  1. Synchrotron radiation macromolecular crystallography: science and spin-offs.

    Science.gov (United States)

    Helliwell, John R; Mitchell, Edward P

    2015-03-01

    A current overview of synchrotron radiation (SR) in macromolecular crystallography (MX) instrumentation, methods and applications is presented. Automation has been and remains a central development in the last decade, as have the rise of remote access and of industrial service provision. Results include a high number of Protein Data Bank depositions, with an increasing emphasis on the successful use of microcrystals. One future emphasis involves pushing the frontiers of using higher and lower photon energies. With the advent of X-ray free-electron lasers, closely linked to SR developments, the use of ever smaller samples such as nanocrystals, nanoclusters and single molecules is anticipated, as well as the opening up of femtosecond time-resolved diffraction structural studies. At SR sources, a very high-throughput assessment for the best crystal samples and the ability to tackle just a few micron and sub-micron crystals will become widespread. With higher speeds and larger detectors, diffraction data volumes are becoming long-term storage and archiving issues; the implications for today and the future are discussed. Together with the rise of the storage ring to its current pre-eminence in MX data provision, the growing tendency of central facility sites to offer other centralized facilities complementary to crystallography, such as cryo-electron microscopy and NMR, is a welcome development.

  2. Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels

    Science.gov (United States)

    Vermonden, Tina; Jena, Sidhartha S.; Barriet, David; Censi, Roberta; van der Gucht, Jasper; Hennink, Wim E.; Siegel, Ronald A.

    2009-01-01

    Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery. PMID:20885989

  3. Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels.

    Science.gov (United States)

    Vermonden, Tina; Jena, Sidhartha S; Barriet, David; Censi, Roberta; van der Gucht, Jasper; Hennink, Wim E; Siegel, Ronald A

    2010-01-26

    Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery.

  4. Adaptation to extreme environments: macromolecular dynamics in bacteria compared in vivo by neutron scattering.

    Science.gov (United States)

    Tehei, Moeava; Franzetti, Bruno; Madern, Dominique; Ginzburg, Margaret; Ginzburg, Ben Z; Giudici-Orticoni, Marie-Thérèse; Bruschi, Mireille; Zaccai, Giuseppe

    2004-01-01

    Mean macromolecular dynamics was quantified in vivo by neutron scattering in psychrophile, mesophile, thermophile and hyperthermophile bacteria. Root mean square atomic fluctuation amplitudes determining macromolecular flexibility were found to be similar for each organism at its physiological temperature ( approximately 1 A in the 0.1 ns timescale). Effective force constants determining the mean macromolecular resilience were found to increase with physiological temperature from 0.2 N/m for the psychrophiles, which grow at 4 degrees C, to 0.6 N/m for the hyperthermophiles (85 degrees C), indicating that the increase in stabilization free energy is dominated by enthalpic rather than entropic terms. Larger resilience allows macromolecular stability at high temperatures, while maintaining flexibility within acceptable limits for biological activity.

  5. Macromolecular 'size' and 'hardness' drives structure in solvent-swollen blends of linear, cyclic, and star polymers.

    Science.gov (United States)

    Gartner, Thomas E; Jayaraman, Arthi

    2018-01-17

    In this paper, we apply molecular simulation and liquid state theory to uncover the structure and thermodynamics of homopolymer blends of the same chemistry and varying chain architecture in the presence of explicit solvent species. We use hybrid Monte Carlo (MC)/molecular dynamics (MD) simulations in the Gibbs ensemble to study the swelling of ∼12 000 g mol -1 linear, cyclic, and 4-arm star polystyrene chains in toluene. Our simulations show that the macroscopic swelling response is indistinguishable between the various architectures and matches published experimental data for the solvent annealing of linear polystyrene by toluene vapor. We then use standard MD simulations in the NPT ensemble along with polymer reference interaction site model (PRISM) theory to calculate effective polymer-solvent and polymer-polymer Flory-Huggins interaction parameters (χ eff ) in these systems. As seen in the macroscopic swelling results, there are no significant differences in the polymer-solvent and polymer-polymer χ eff between the various architectures. Despite similar macroscopic swelling and effective interaction parameters between various architectures, the pair correlation function between chain centers-of-mass indicates stronger correlations between cyclic or star chains in the linear-cyclic blends and linear-star blends, compared to linear chain-linear chain correlations. Furthermore, we note striking similarities in the chain-level correlations and the radius of gyration of cyclic and 4-arm star architectures of identical molecular weight. Our results indicate that the cyclic and star chains are 'smaller' and 'harder' than their linear counterparts, and through comparison with MD simulations of blends of soft spheres with varying hardness and size we suggest that these macromolecular characteristics are the source of the stronger cyclic-cyclic and star-star correlations.

  6. Computational models of complex systems

    CERN Document Server

    Dabbaghian, Vahid

    2014-01-01

    Computational and mathematical models provide us with the opportunities to investigate the complexities of real world problems. They allow us to apply our best analytical methods to define problems in a clearly mathematical manner and exhaustively test our solutions before committing expensive resources. This is made possible by assuming parameter(s) in a bounded environment, allowing for controllable experimentation, not always possible in live scenarios. For example, simulation of computational models allows the testing of theories in a manner that is both fundamentally deductive and experimental in nature. The main ingredients for such research ideas come from multiple disciplines and the importance of interdisciplinary research is well recognized by the scientific community. This book provides a window to the novel endeavours of the research communities to present their works by highlighting the value of computational modelling as a research tool when investigating complex systems. We hope that the reader...

  7. Model reduction of parametrized systems

    CERN Document Server

    Ohlberger, Mario; Patera, Anthony; Rozza, Gianluigi; Urban, Karsten

    2017-01-01

    The special volume offers a global guide to new concepts and approaches concerning the following topics: reduced basis methods, proper orthogonal decomposition, proper generalized decomposition, approximation theory related to model reduction, learning theory and compressed sensing, stochastic and high-dimensional problems, system-theoretic methods, nonlinear model reduction, reduction of coupled problems/multiphysics, optimization and optimal control, state estimation and control, reduced order models and domain decomposition methods, Krylov-subspace and interpolatory methods, and applications to real industrial and complex problems. The book represents the state of the art in the development of reduced order methods. It contains contributions from internationally respected experts, guaranteeing a wide range of expertise and topics. Further, it reflects an important effor t, carried out over the last 12 years, to build a growing research community in this field. Though not a textbook, some of the chapters ca...

  8. Sulfation by human lung fibroblasts: SO4(2-) and sulfur-containing amino acids as sources for macromolecular sulfation.

    Science.gov (United States)

    Elgavish, A; Meezan, E

    1991-06-01

    Studies were carried out in human lung fibroblasts (IMR-90) to investigate 1) the relative contribution of two extracellular pools, inorganic sulfate and sulfur-containing amino acids, to the intracellular fraction precipitable by trichloroacetic acid and 2) the possibility that the transport of these sulfur-containing substrates at the plasma membrane may be a limiting step for macromolecular sulfation. Our studies indicate that the ability to use SO4(2-) released by intracellular catabolism of the sulfur-containing amino acid L-cysteine differs from one cell system to another. In contrast to smooth muscle cells, in the human lung fibroblast, L-cysteine contributes significantly to the intercellular pool of SO4(2-) used for sulfation at extracellular [SO4(2-)] less than 100 microM. However, under physiological conditions with respect to SO4(2-) ([SO4(2-)]0 = 300 microM), L-cysteine does not contribute greater than 30% of the sulfate incorporated into the cellular fraction. Taurine (2-aminoethanesulfonic acid) inhibits SO4(2-) incorporation into the cell-associated macromolecular fraction. However, results suggest that the effect is not due to either SO4(2-) released by its catabolism or to an effect on SO4(2-) transport into the cell. The fact that the transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibits sulfate incorporation indicates that carrier-mediated sulfate transport at the cellular plasma membrane may be a limiting step for sulfate incorporation. In conclusion, under physiological conditions with respect to SO4(2-), inorganic sulfate is a major source of sulfate for sulfation in human lung fibroblasts and macromolecular sulfation may be limited by its transport into the cells.

  9. Modeling software systems by domains

    Science.gov (United States)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  10. 7T Magnetization Transfer and Chemical Exchange Saturation Transfer MRI of Cortical Gray Matter: Can We Detect Neurochemical and Macromolecular Abnormalities?

    Science.gov (United States)

    2014-10-21

    CPU). Theoretical saturation was modeled according to the Bloch equations for three pools: bulk water ( free ), semisolid macromolecular (conventional...concentration of semi-solid components (MT) at constant pH. These phantoms include: glutamate, myoinositol, glycogen , bovine serum albumin (BSA...TFE factor 256 3D free factor no startup echoes default Act. WFS (pix) / BW (Hz) Min. WFS (pix) / Max. BW (Hz) 0.579 / 1750.7 0.575

  11. Cognitive models embedded in system simulation models

    International Nuclear Information System (INIS)

    Siegel, A.I.; Wolf, J.J.

    1982-01-01

    If we are to discuss and consider cognitive models, we must first come to grips with two questions: (1) What is cognition; (2) What is a model. Presumably, the answers to these questions can provide a basis for defining a cognitive model. Accordingly, this paper first places these two questions into perspective. Then, cognitive models are set within the context of computer simulation models and a number of computer simulations of cognitive processes are described. Finally, pervasive issues are discussed vis-a-vis cognitive modeling in the computer simulation context

  12. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    . Contrary to earlier theories, the oil is not only present on the surface, but also in great volumes both in the water column and on the seafloor, which indicates that we do not know enough about how oil behaves in water and interacts with it. Sonar detection is one of the most important and necessary...... after an oil spill. Engineering thermodynamics could be applied in the state-of-the-art sonar products through advanced artificial technology, if the speed of sound, solubility and density of oil-seawater systems could be satisfactorily modelled. The addition of methanol or glycols into unprocessed well...... streams during subsea pipelines is necessary to inhibit gas hydrate formation, and the offshore reservoirs often mean complicated temperature and pressure conditions. Accurate description of the phase behavior and thermalphysical properties of complex systems containing petroleum fluids and polar...

  13. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    of the Cu/ZnO nanoparticles is highly relevant to industrial methanol synthesis for which the direct interaction of Cu and ZnO nanocrystals synergistically boost the catalytic activity. The dynamical behavior of the nanoparticles under reducing and oxidizing environments were studied by means of ex situ X...... as the nanoparticles are reduced. The Cu/ZnO nanoparticles are tested on a  µ-reactor platform and prove to be active towards methanol synthesis, making it an excellent model system for further investigations into activity depended morphology changes....

  14. Macromolecular compositions of phytoplankton in the Amundsen Sea, Antarctica

    Science.gov (United States)

    Kim, Bo Kyung; Lee, Jang Han; Joo, HuiTae; Song, Ho Jung; Yang, Eun Jin; Lee, Sang Hoon; Lee, Sang H.

    2016-01-01

    The biochemical compositions (proteins, carbohydrates, and lipids) of phytoplankton provide useful information for their environmental growth conditions and nutritional status as a basic food source for upper trophic consumers. Concentrations of these compositions were assessed at 100, 30, and 1% light penetration depths within the euphotic zone in the Amundsen Sea, Antarctica, using colorimetric techniques. The major inorganic nutrients were generally abundant throughout the study area. The average chlorophyll a (chl-a) concentration was 49.2 mg m-2 (S.D.=±27.6 mg m-2) and large phytoplankton (>20 μm) accounted for 64.1% of the total chl-a concentration. The biochemical compositions of the phytoplankton were not significantly different among different light depths or productivity stations. The overall compositions of proteins, carbohydrates, and lipids from all stations averaged 65.9% (S.D.=±12.5%), 22.4% (S.D.=±10.9%), and 11.7% (S.D.=±6.5%), respectively. Regardless of dominant phytoplankton species, nitrogen-abundant conditions sustained high protein compositions of phytoplankton in the Amundsen Sea during the cruise period. Based on the macromolecular compositions, the average food material (FM) concentration was 219.4 μg L-1 (S.D.=±151.1 μg L-1) and correlated positively with the primary productivity in the Amundsen Sea. High protein/carbohydrate ratios (>1) and large proportions of proteins suggest that phytoplankton provide nitrogen-sufficient foods to higher trophic consumers through a higher efficiency of protein carbon incorporated into herbivores.

  15. Reservoir Model Information System: REMIS

    Science.gov (United States)

    Lee, Sang Yun; Lee, Kwang-Wu; Rhee, Taehyun; Neumann, Ulrich

    2009-01-01

    We describe a novel data visualization framework named Reservoir Model Information System (REMIS) for the display of complex and multi-dimensional data sets in oil reservoirs. It is aimed at facilitating visual exploration and analysis of data sets as well as user collaboration in an easier way. Our framework consists of two main modules: the data access point module and the data visualization module. For the data access point module, the Phrase-Driven Grammar System (PDGS) is adopted for helping users facilitate the visualization of data. It integrates data source applications and external visualization tools and allows users to formulate data query and visualization descriptions by selecting graphical icons in a menu or on a map with step-by-step visual guidance. For the data visualization module, we implemented our first prototype of an interactive volume viewer named REMVR to classify and to visualize geo-spatial specific data sets. By combining PDGS and REMVR, REMIS assists users better in describing visualizations and exploring data so that they can easily find desired data and explore interesting or meaningful relationships including trends and exceptions in oil reservoir model data.

  16. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  17. Large area high-resolution CCD-based X-ray detector for macromolecular crystallography

    CERN Document Server

    Pokric, M; Jorden, A R; Cox, M P; Marshall, A; Long, P G; Moon, K; Jerram, P A; Pool, P; Nave, C; Derbyshire, G E; Helliwell, J R

    2002-01-01

    An X-ray detector system for macromolecular crystallography based on a large area charge-coupled device (CCD) sensor has been developed as part of a large research and development programme for advanced X-ray sensor technology, funded by industry and the Particle Physics and Astronomy Research Council (PPARC) in the UK. The prototype detector consists of two large area three-sides buttable charge-coupled devices (CCD 46-62 EEV), where the single CCD area is 55.3 mmx41.5 mm. Overall detector imaging area is easily extendable to 85 mmx110 mm. The detector consists of an optically coupled X-ray sensitive phosphor, skewed fibre-optic studs and CCDs. The crystallographic measurement requirements at synchrotron sources are met through a high spatial resolution (2048x1536 pixel array), high dynamic range (approx 10 sup 5), a fast readout (approx 1 s), low noise (<10e sup -) and much reduced parallax error. Additionally, the prototype detector system has been optimised by increasing its efficiency at low X-ray ene...

  18. Bond graph modeling of centrifugal compression systems

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2015-01-01

    A novel approach to model unsteady fluid dynamics in a compressor network by using a bond graph is presented. The model is intended in particular for compressor control system development. First, we develop a bond graph model of a single compression system. Bond graph modeling offers a different perspective to previous work by modeling the compression system based on energy flow instead of fluid dynamics. Analyzing the bond graph model explains the energy flow during compressor surge. Two pri...

  19. Structuring Problem Analysis for Embedded Systems Modelling

    NARCIS (Netherlands)

    Marincic, J.; Mader, Angelika H.; Wieringa, Roelf J.; Lucas, Yan

    Our interest is embedded systems validation as part of the model-driven approach. To design a model, the modeller needs to obtain knowledge about the system and decide what is relevant to model and how. A part of the modelling activities is inherently informal - it cannot be formalised in such a way

  20. Importance of Excluded Volume and Hydrodynamic Interactions on Macromolecular Diffusion in Vivo

    Science.gov (United States)

    Ando, Tadashi; Skolnick, Jeffrey

    2013-01-01

    The interiors of all living cells are highly crowded with macromolecules, which results in a considerable difference between the thermodynamics and kinetics of biological reactions in vivo from that in vitro. To begin to elucidate the principles of intermolecular dynamics in the crowded environment of cells, employing Brownian dynamics (BD) simulations, we examined possible mechanism(s) responsible for the great reduction in diffusion constants of macromolecules in vivo from that at infinite dilution. In an E. coli cytoplasm model comprised of 15 different macromolecule types at physiological concentrations, where macromolecules were represented by spheres with their Stokes radii, BD simulations were performed with and without hydrodynamic interactions (HI). Without HI, the calculated diffusion constant of green fluorescent protein (GFP) is much larger than experiment. On the other hand, when HI were considered, the in vivo experimental GFP diffusion constant is almost reproduced without adjustable parameters. In addition, HI give rise to significant, size independent intermolecular dynamic correlations. These results suggest that HI play an important role on macromolecular dynamics in vivo.

  1. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  2. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography.

    Science.gov (United States)

    Chen, Julian C-H; Unkefer, Clifford J

    2017-01-01

    The Protein Crystallography Station (PCS), located at the Los Alamos Neutron Scattering Center (LANSCE), was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER) for 13 years (2002-2014). The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallo-graphy in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  3. Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

    2017-02-01

    Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  4. MetalPDB: a database of metal sites in biological macromolecular structures.

    Science.gov (United States)

    Andreini, Claudia; Cavallaro, Gabriele; Lorenzini, Serena; Rosato, Antonio

    2013-01-01

    We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a novel resource aimed at conveying the information available on the three-dimensional (3D) structures of metal-binding biological macromolecules in a consistent and effective manner. This is achieved through the systematic and automated representation of metal-binding sites in proteins and nucleic acids by way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure embedding the site(s), and are the central objects of MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites found in corresponding positions in similar structures) and equivalent sites (equistructural sites that contain the same metals), allowing users to easily analyse similarities and variations in metal-macromolecule interactions, and to link them to functional information. The web interface of MetalPDB allows access to a comprehensive overview of metal-containing biological structures, providing a basis to investigate the basic principles governing the properties of these systems. MetalPDB is updated monthly in an automated manner.

  5. Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

    Science.gov (United States)

    Palermo, Vincenzo; Schwartz, Erik; Finlayson, Chris E; Liscio, Andrea; Otten, Matthijs B J; Trapani, Sara; Müllen, Klaus; Beljonne, David; Friend, Richard H; Nolte, Roeland J M; Rowan, Alan E; Samorì, Paolo

    2010-02-23

    The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

  6. Cooperative polymerization of α-helices induced by macromolecular architecture

    Science.gov (United States)

    Baumgartner, Ryan; Fu, Hailin; Song, Ziyuan; Lin, Yao; Cheng, Jianjun

    2017-07-01

    Catalysis observed in enzymatic processes and protein polymerizations often relies on the use of supramolecular interactions and the organization of functional elements in order to gain control over the spatial and temporal elements of fundamental cellular processes. Harnessing these cooperative interactions to catalyse reactions in synthetic systems, however, remains challenging due to the difficulty in creating structurally controlled macromolecules. Here, we report a polypeptide-based macromolecule with spatially organized α-helices that can catalyse its own formation. The system consists of a linear polymeric scaffold containing a high density of initiating groups from which polypeptides are grown, forming a brush polymer. The folding of polypeptide side chains into α-helices dramatically enhances the polymerization rate due to cooperative interactions of macrodipoles between neighbouring α-helices. The parameters that affect the rate are elucidated by a two-stage kinetic model using principles from nucleation-controlled protein polymerizations; the key difference being the irreversible nature of this polymerization.

  7. Visual computing model for immune system and medical system.

    Science.gov (United States)

    Gong, Tao; Cao, Xinxue; Xiong, Qin

    2015-01-01

    Natural immune system is an intelligent self-organizing and adaptive system, which has a variety of immune cells with different types of immune mechanisms. The mutual cooperation between the immune cells shows the intelligence of this immune system, and modeling this immune system has an important significance in medical science and engineering. In order to build a comprehensible model of this immune system for better understanding with the visualization method than the traditional mathematic model, a visual computing model of this immune system was proposed and also used to design a medical system with the immune system, in this paper. Some visual simulations of the immune system were made to test the visual effect. The experimental results of the simulations show that the visual modeling approach can provide a more effective way for analyzing this immune system than only the traditional mathematic equations.

  8. Model Information Exchange System (MIXS).

    Science.gov (United States)

    2013-08-01

    Many travel demand forecast models operate at state, regional, and local levels. While they share the same physical network in overlapping geographic areas, they use different and uncoordinated modeling networks. This creates difficulties for models ...

  9. Two sustainable energy system analysis models

    DEFF Research Database (Denmark)

    Lund, Henrik; Goran Krajacic, Neven Duic; da Graca Carvalho, Maria

    2005-01-01

    This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy.......This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy....

  10. Models for multimegawatt space power systems

    Energy Technology Data Exchange (ETDEWEB)

    Edenburn, M.W.

    1990-06-01

    This report describes models for multimegawatt, space power systems which Sandia's Advanced Power Systems Division has constructed to help evaluate space power systems for SDI's Space Power Office. Five system models and models for associated components are presented for both open (power system waste products are exhausted into space) and closed (no waste products) systems: open, burst mode, hydrogen cooled nuclear reactor -- turboalternator system; open, hydrogen-oxygen combustion turboalternator system; closed, nuclear reactor powered Brayton cycle system; closed, liquid metal Rankine cycle system; and closed, in-core, reactor therminonic system. The models estimate performance and mass for the components in each of these systems. 17 refs., 8 figs., 15 tabs.

  11. The effect of macromolecular crowding on mobility of biomolecules, association kinetics and gene expression in living cells

    Science.gov (United States)

    Tabaka, Marcin; Kalwarczyk, Tomasz; Szymanski, Jedrzej; Hou, Sen; Hołyst, Robert

    2014-09-01

    We discuss a quantitative influence of macromolecular crowding on biological processes: motion, bimolecular reactions, and gene expression in prokaryotic and eukaryotic cells. We present scaling laws relating diffusion coefficient of an object moving in a cytoplasm of cells to a size of this object and degree of crowding. Such description leads to the notion of the length scale dependent viscosity characteristic for all living cells. We present an application of the length-scale dependent viscosity model to the description of motion in the cytoplasm of both eukaryotic and prokaryotic living cells. We compare the model with all recent data on diffusion of nanoscopic objects in HeLa, and E. coli cells. Additionally a description of the mobility of molecules in cell nucleus is presented. Finally we discuss the influence of crowding on the bimolecular association rates and gene expression in living cells.

  12. The use of a mini-κ goniometer head in macromolecular crystallography diffraction experiments.

    Science.gov (United States)

    Brockhauser, Sandor; Ravelli, Raimond B G; McCarthy, Andrew A

    2013-07-01

    Most macromolecular crystallography (MX) diffraction experiments at synchrotrons use a single-axis goniometer. This markedly contrasts with small-molecule crystallography, in which the majority of the diffraction data are collected using multi-axis goniometers. A novel miniaturized κ-goniometer head, the MK3, has been developed to allow macromolecular crystals to be aligned. It is available on the majority of the structural biology beamlines at the ESRF, as well as elsewhere. In addition, the Strategy for the Alignment of Crystals (STAC) software package has been developed to facilitate the use of the MK3 and other similar devices. Use of the MK3 and STAC is streamlined by their incorporation into online analysis tools such as EDNA. The current use of STAC and MK3 on the MX beamlines at the ESRF is discussed. It is shown that the alignment of macromolecular crystals can result in improved diffraction data quality compared with data obtained from randomly aligned crystals.

  13. Modeling traceability in system of systems

    NARCIS (Netherlands)

    Tekinerdogan, Bedir; Erata, Ferhat

    2017-01-01

    An important aspect in SoS is the realization of the concerns in different systems that work together. Identifying and locating these concerns is important to orchestrate the overall activities and hereby to achieve the overall goal of the SoS. Moreover, concerns in SoS are rarely stable and need

  14. Modeling of Nonlinear Systems using Genetic Algorithm

    Science.gov (United States)

    Hayashi, Kayoko; Yamamoto, Toru; Kawada, Kazuo

    In this paper, a newly modeling system by using Genetic Algorithm (GA) is proposed. The GA is an evolutionary computational method that simulates the mechanisms of heredity or evolution of living things, and it is utilized in optimization and in searching for optimized solutions. Most process systems have nonlinearities, so it is necessary to anticipate exactly such systems. However, it is difficult to make a suitable model for nonlinear systems, because most nonlinear systems have a complex structure. Therefore the newly proposed method of modeling for nonlinear systems uses GA. Then, according to the newly proposed scheme, the optimal structure and parameters of the nonlinear model are automatically generated.

  15. Model Driven Development of Data Sensitive Systems

    DEFF Research Database (Denmark)

    Olsen, Petur

    2014-01-01

    to the values of variables. This theses strives to improve model-driven development of such data-sensitive systems. This is done by addressing three research questions. In the first we combine state-based modeling and abstract interpretation, in order to ease modeling of data-sensitive systems, while allowing...... efficient model-checking and model-based testing. In the second we develop automatic abstraction learning used together with model learning, in order to allow fully automatic learning of data-sensitive systems to allow learning of larger systems. In the third we develop an approach for modeling and model-based...... detection and pushing error detection to earlier stages of development. The complexity of modeling and the size of systems which can be analyzed is severely limited when introducing data variables. The state space grows exponentially in the number of variable and the domain size of the variables...

  16. Modeling of a Hydraulic Braking System

    OpenAIRE

    Lundin, Christopher

    2015-01-01

    The objective of this thesis is to derive an analytical model representing a reduced form of a mine hoist hydraulic braking system. Based primarily on fluid mechanical and mechanical physical modeling, along with a number of simplifying assumptions, the analytical model will be derived and expressed in the form of a system of differential equations including a set of static functions. The obtained model will be suitable for basic simulation and analysis of system dynamics, with the aim to cap...

  17. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin

    2010-01-01

    Model Driven Software Development has offered a faster way to design and implement embedded real-time software by moving the design to a model level, and by transforming models to code. However, the testing of embedded systems has remained at the code level. This paper presents a Graphical Model...... Debugger Framework, providing an auxiliary avenue of analysis of system models at runtime by executing generated code and updating models synchronously, which allows embedded developers to focus on the model level. With the model debugger, embedded developers can graphically test their design model...... and check the running status of the system, which offers a debugging capability on a higher level of abstraction. The framework intends to contribute a tool to the Eclipse society, especially suitable for model-driven development of embedded systems....

  18. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  19. An acoustic on-chip goniometer for room temperature macromolecular crystallography.

    Science.gov (United States)

    Burton, C G; Axford, D; Edwards, A M J; Gildea, R J; Morris, R H; Newton, M I; Orville, A M; Prince, M; Topham, P D; Docker, P T

    2017-12-05

    This paper describes the design, development and successful use of an on-chip goniometer for room-temperature macromolecular crystallography via acoustically induced rotations. We present for the first time a low cost, rate-tunable, acoustic actuator for gradual in-fluid sample reorientation about varying axes and its utilisation for protein structure determination on a synchrotron beamline. The device enables the efficient collection of diffraction data via a rotation method from a sample within a surface confined droplet. This method facilitates efficient macromolecular structural data acquisition in fluid environments for dynamical studies.

  20. Hydrological modelling in forested systems

    Science.gov (United States)

    This chapter provides a brief overview of forest hydrology modelling approaches for answering important global research and management questions. Many hundreds of hydrological models have been applied globally across multiple decades to represent and predict forest hydrological p...

  1. Towards Modelling of Hybrid Systems

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2006-01-01

    The article is an attempt to use methods of category theory and topology for analysis of hybrid systems. We use the notion of a directed topological space; it is a topological space together with a set of privileged paths. Dynamical systems are examples of directed topological spaces. A hybrid...... system consists of a number of dynamical systems that are glued together according to information encoded in the discrete part of the system. We develop a definition of a hybrid system as a functor from the category generated by a transition system to the category of directed topological spaces. Its...... directed homotopy colimit (geometric realization) is a single directed topological space. The behavior of hybrid systems can be then understood in terms of the behavior of dynamical systems through the directed homotopy colimit....

  2. Room-temperature macromolecular serial crystallography using synchrotron radiation

    Directory of Open Access Journals (Sweden)

    Francesco Stellato

    2014-07-01

    Full Text Available A new approach for collecting data from many hundreds of thousands of microcrystals using X-ray pulses from a free-electron laser has recently been developed. Referred to as serial crystallography, diffraction patterns are recorded at a constant rate as a suspension of protein crystals flows across the path of an X-ray beam. Events that by chance contain single-crystal diffraction patterns are retained, then indexed and merged to form a three-dimensional set of reflection intensities for structure determination. This approach relies upon several innovations: an intense X-ray beam; a fast detector system; a means to rapidly flow a suspension of crystals across the X-ray beam; and the computational infrastructure to process the large volume of data. Originally conceived for radiation-damage-free measurements with ultrafast X-ray pulses, the same methods can be employed with synchrotron radiation. As in powder diffraction, the averaging of thousands of observations per Bragg peak may improve the ratio of signal to noise of low-dose exposures. Here, it is shown that this paradigm can be implemented for room-temperature data collection using synchrotron radiation and exposure times of less than 3 ms. Using lysozyme microcrystals as a model system, over 40 000 single-crystal diffraction patterns were obtained and merged to produce a structural model that could be refined to 2.1 Å resolution. The resulting electron density is in excellent agreement with that obtained using standard X-ray data collection techniques. With further improvements the method is well suited for even shorter exposures at future and upgraded synchrotron radiation facilities that may deliver beams with 1000 times higher brightness than they currently produce.

  3. Service systems concepts, modeling, and programming

    CERN Document Server

    Cardoso, Jorge; Poels, Geert

    2014-01-01

    This SpringerBrief explores the internal workings of service systems. The authors propose a lightweight semantic model for an effective representation to capture the essence of service systems. Key topics include modeling frameworks, service descriptions and linked data, creating service instances, tool support, and applications in enterprises.Previous books on service system modeling and various streams of scientific developments used an external perspective to describe how systems can be integrated. This brief introduces the concept of white-box service system modeling as an approach to mo

  4. On Verification Modelling of Embedded Systems

    NARCIS (Netherlands)

    Brinksma, Hendrik; Mader, Angelika H.

    Computer-aided verification of embedded systems hinges on the availability of good verification models of the systems at hand. Such models must be much simpler than full design models or specifications to be of practical value, because of the unavoidable combinatorial complexities in the

  5. Balmorel open source energy system model

    DEFF Research Database (Denmark)

    Wiese, Frauke; Bramstoft, Rasmus; Koduvere, Hardi

    2018-01-01

    As the world progresses towards a cleaner energy future with more variable renewable energy sources, energy system models are required to deal with new challenges. This article describes design, development and applications of the open source energy system model Balmorel, which is a result of a l...... transport of local biomass as part of the optimisation and speeding up the model....

  6. Modeling, Control and Coordination of Helicopter Systems

    CERN Document Server

    Ren, Beibei; Chen, Chang; Fua, Cheng-Heng; Lee, Tong Heng

    2012-01-01

    Modeling, Control and Coordination of Helicopter Systems provides a comprehensive treatment of helicopter systems, ranging from related nonlinear flight dynamic modeling and stability analysis to advanced control design for single helicopter systems, and also covers issues related to the coordination and formation control of multiple helicopter systems to achieve high performance tasks. Ensuring stability in helicopter flight is a challenging problem for nonlinear control design and development. This book is a valuable reference on modeling, control and coordination of helicopter systems,providing readers with practical solutions for the problems that still plague helicopter system design and implementation. Readers will gain a complete picture of helicopters at the systems level, as well as a better understanding of the technical intricacies involved. This book also: Presents a complete picture of modeling, control and coordination for helicopter systems Provides a modeling platform for a general class of ro...

  7. Systems Biology—Biomedical Modeling

    OpenAIRE

    Sobie, Eric A.; Lee, Young-Seon; Jenkins, Sherry L.; Iyengar, Ravi

    2011-01-01

    Because of the complexity inherent in biological systems, many researchers frequently rely on a combination of global analysis and computational approaches to gain insight into both (i) how interacting components can produce complex system behaviors, and (ii) how changes in conditions may alter these behaviors. Because the biological details of a particular system are generally not taught along with the quantitative approaches that enable hypothesis generation and analysis of the system, we d...

  8. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

    Science.gov (United States)

    Foffi, G; Pastore, A; Piazza, F; Temussi, P A

    2013-08-02

    conference held in Ascona from 10 to 14 June 2012. In the unique scenario of the Maggiore lake and absorbed in the magic atmosphere of the Centro Stefano Franscini (CSF) at Monte Verità, we enjoyed three-and-a-half days of intense and inspiring activity, where not only many of the most prominent scientists working on macromolecular crowding, but also experts in closely related fields such as colloids and soft matter presented their work. The meeting was intended and has been organized to bring theoreticians and experimentalists together in the attempt to promote an active dialogue. Moreover, we wanted different disciplines to be represented, notably physics and chemistry, besides biology, as cross-fertilization is proving an increasingly fundamental source of inspiration and advancement. This issue of Physical Biology (PB) features a selection of the oral contributions presented at the conference, expanded in the form of research or review articles. PB, one of the scientific journals of the Institute of Physics (IOP), is one of the most dynamic and lively forums active at the interface between biology on one side, and physics and mathematics on the other. As its mission is stated by IOP, PB 'focuses on research in which physics-based approaches lead to new insights into biological systems at all scales of space and time, and all levels of complexity'. For these reasons, and also in view of its high reputation and broad readership, PB appears to be the ideal place for disseminating the thriving pieces of research presented at the conference. We are extremely grateful to PB and its kind and efficient editorial staff who helped make this issue a great scientific follow-up to the conference. The opening lecture of the conference, the first of four day-opening keynote lectures, was given by Allen P Minton from NIH (USA), possibly the most influential among the pioneers in the field. He provided a lucid and well-thought-out overview of the concept of macromolecular crowding

  9. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012)

    Science.gov (United States)

    Foffi, G.; Pastore, A.; Piazza, F.; Temussi, P. A.

    2013-08-01

    held in Ascona from 10 to 14 June 2012. In the unique scenario of the Maggiore lake and absorbed in the magic atmosphere of the Centro Stefano Franscini (CSF) at Monte Verità, we enjoyed three-and-a-half days of intense and inspiring activity, where not only many of the most prominent scientists working on macromolecular crowding, but also experts in closely related fields such as colloids and soft matter presented their work. The meeting was intended and has been organized to bring theoreticians and experimentalists together in the attempt to promote an active dialogue. Moreover, we wanted different disciplines to be represented, notably physics and chemistry, besides biology, as cross-fertilization is proving an increasingly fundamental source of inspiration and advancement. This issue of Physical Biology (PB) features a selection of the oral contributions presented at the conference, expanded in the form of research or review articles. PB, one of the scientific journals of the Institute of Physics (IOP), is one of the most dynamic and lively forums active at the interface between biology on one side, and physics and mathematics on the other. As its mission is stated by IOP, PB 'focuses on research in which physics-based approaches lead to new insights into biological systems at all scales of space and time, and all levels of complexity'. For these reasons, and also in view of its high reputation and broad readership, PB appears to be the ideal place for disseminating the thriving pieces of research presented at the conference. We are extremely grateful to PB and its kind and efficient editorial staff who helped make this issue a great scientific follow-up to the conference. The opening lecture of the conference, the first of four day-opening keynote lectures, was given by Allen P Minton from NIH (USA), possibly the most influential among the pioneers in the field. He provided a lucid and well-thought-out overview of the concept of macromolecular crowding through an

  10. Modeling and simulation of systems using Matlab and Simulink

    CERN Document Server

    Chaturvedi, Devendra K

    2009-01-01

    Introduction to SystemsSystemClassification of SystemsLinear SystemsTime-Varying vs. Time-Invariant Systems Lumped vs. Distributed Parameter SystemsContinuous- and Discrete-Time Systems Deterministic vs. Stochastic Systems Hard and Soft Systems Analysis of Systems Synthesis of Systems Introduction to System Philosophy System Thinking Large and Complex Applied System Engineering: A Generic ModelingSystems ModelingIntroduction Need of System Modeling Modeling Methods for Complex Systems Classification of ModelsCharacteristics of Models ModelingMathematical Modeling of Physical SystemsFormulation of State Space Model of SystemsPhysical Systems Theory System Components and Interconnections Computation of Parameters of a Component Single Port and Multiport Systems Techniques of System Analysis Basics of Linear Graph Theoretic ApproachFormulation of System Model for Conceptual SystemFormulation System Model for Physical SystemsTopological RestrictionsDevelopment of State Model of Degenerative SystemSolution of Stat...

  11. Modelling and Verification of Relay Interlocking Systems

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth; Bliguet, Marie Le; Kjær, Andreas

    2010-01-01

    This paper describes how relay interlocking systems as used by the Danish railways can be formally modelled and verified. Such systems are documented by circuit diagrams describing their static layout. It is explained how to derive a state transition system model for the dynamic behaviour of a re...

  12. Compositional Modelling of Stochastic Hybrid Systems

    NARCIS (Netherlands)

    Strubbe, S.N.

    2005-01-01

    In this thesis we present a modelling framework for compositional modelling of stochastic hybrid systems. Hybrid systems consist of a combination of continuous and discrete dynamics. The state space of a hybrid system is hybrid in the sense that it consists of a continuous component and a discrete

  13. MolProbity: all-atom structure validation for macromolecular crystallography

    International Nuclear Information System (INIS)

    Chen, Vincent B.; Arendall, W. Bryan III; Headd, Jeffrey J.; Keedy, Daniel A.; Immormino, Robert M.; Kapral, Gary J.; Murray, Laura W.; Richardson, Jane S.; Richardson, David C.

    2010-01-01

    MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction. MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors’ contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database

  14. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations, understa......Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations......, understanding them as embedded into a wider attitude system that consists of attitudes towards objects of different abstraction levels, ranging from personal value orientations over general socio-political attitudes to evaluations of specific characteristics of agricultural production systems. It is assumed...... that evaluative affect propagates through the system in such a way that the system becomes evaluatively consistent and operates as a schema for the generation of evaluative judgments. In the empirical part of the paper, the causal structure of an attitude system from which people derive their evaluations of pork...

  15. The use of workflows in the design and implementation of complex experiments in macromolecular crystallography

    International Nuclear Information System (INIS)

    Brockhauser, Sandor; Svensson, Olof; Bowler, Matthew W.; Nanao, Max; Gordon, Elspeth; Leal, Ricardo M. F.; Popov, Alexander; Gerring, Matthew; McCarthy, Andrew A.; Gotz, Andy

    2012-01-01

    A powerful and easy-to-use workflow environment has been developed at the ESRF for combining experiment control with online data analysis on synchrotron beamlines. This tool provides the possibility of automating complex experiments without the need for expertise in instrumentation control and programming, but rather by accessing defined beamline services. The automation of beam delivery, sample handling and data analysis, together with increasing photon flux, diminishing focal spot size and the appearance of fast-readout detectors on synchrotron beamlines, have changed the way that many macromolecular crystallography experiments are planned and executed. Screening for the best diffracting crystal, or even the best diffracting part of a selected crystal, has been enabled by the development of microfocus beams, precise goniometers and fast-readout detectors that all require rapid feedback from the initial processing of images in order to be effective. All of these advances require the coupling of data feedback to the experimental control system and depend on immediate online data-analysis results during the experiment. To facilitate this, a Data Analysis WorkBench (DAWB) for the flexible creation of complex automated protocols has been developed. Here, example workflows designed and implemented using DAWB are presented for enhanced multi-step crystal characterizations, experiments involving crystal reorientation with kappa goniometers, crystal-burning experiments for empirically determining the radiation sensitivity of a crystal system and the application of mesh scans to find the best location of a crystal to obtain the highest diffraction quality. Beamline users interact with the prepared workflows through a specific brick within the beamline-control GUI MXCuBE

  16. Modeling Control Situations in Power System Operations

    DEFF Research Database (Denmark)

    Saleem, Arshad; Lind, Morten; Singh, Sri Niwas

    2010-01-01

    Increased interconnection and loading of the power system along with deregulation has brought new challenges for electric power system operation, control and automation. Traditional power system models used in intelligent operation and control are highly dependent on the task purpose. Thus, a model...... of explicit principles for model construction. This paper presents a work on using explicit means-ends model based reasoning about complex control situations which results in maintaining consistent perspectives and selecting appropriate control action for goal driven agents. An example of power system...... for intelligent operation and control must represent system features, so that information from measurements can be related to possible system states and to control actions. These general modeling requirements are well understood, but it is, in general, difficult to translate them into a model because of the lack...

  17. Holonic Models for Traffic Control Systems

    Science.gov (United States)

    Ciufudean, Calin; Filote, Constantin

    This paper proposes a new time-placed net model for traffic control systems, respectively railway control traffic systems. This model can be interpreted as a holonic one, and contains three modules: Transport Planning Module, Transport Control Module and Priority Control Module. For railway traffic systems we introduce a strategy in a timed-place Petri net model to solve collision and traffic jam problems.

  18. Hydrological modeling in forested systems

    Science.gov (United States)

    H.E. Golden; G.R. Evenson; S. Tian; Devendra Amatya; Ge Sun

    2015-01-01

    Characterizing and quantifying interactions among components of the forest hydrological cycle is complex and usually requires a combination of field monitoring and modelling approaches (Weiler and McDonnell, 2004; National Research Council, 2008). Models are important tools for testing hypotheses, understanding hydrological processes and synthesizing experimental data...

  19. KinImmerse: Macromolecular VR for NMR ensembles

    Directory of Open Access Journals (Sweden)

    Vinson E Claire

    2009-02-01

    Full Text Available Abstract Background In molecular applications, virtual reality (VR and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case. Methods The Syzygy open-source toolkit for VR software was used to write the KinImmerse program, which translates the molecular capabilities of the kinemage graphics format into software for display and manipulation in the DiVE (Duke immersive Virtual Environment or other VR system. KinImmerse is supported by the flexible display construction and editing features in the KiNG kinemage viewer and it implements new forms of user interaction in the DiVE. Results In addition to molecular visualizations and navigation, KinImmerse provides a set of research tools for manipulation, identification, co-centering of multiple models, free-form 3D annotation, and output of results. The molecular research test case analyzes the local neighborhood around an individual atom within an ensemble of nuclear magnetic resonance (NMR models, enabling immersive visual comparison of the local conformation with the local NMR experimental data, including target curves for residual dipolar couplings (RDCs. Conclusion The promise of KinImmerse for production-level molecular research in the DiVE is shown by the locally co-centered RDC visualization developed there, which gave new insights now being pursued in wider data analysis.

  20. Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive.

    Science.gov (United States)

    Burley, Stephen K; Berman, Helen M; Kleywegt, Gerard J; Markley, John L; Nakamura, Haruki; Velankar, Sameer

    2017-01-01

    The Protein Data Bank (PDB)--the single global repository of experimentally determined 3D structures of biological macromolecules and their complexes--was established in 1971, becoming the first open-access digital resource in the biological sciences. The PDB archive currently houses ~130,000 entries (May 2017). It is managed by the Worldwide Protein Data Bank organization (wwPDB; wwpdb.org), which includes the RCSB Protein Data Bank (RCSB PDB; rcsb.org), the Protein Data Bank Japan (PDBj; pdbj.org), the Protein Data Bank in Europe (PDBe; pdbe.org), and BioMagResBank (BMRB; www.bmrb.wisc.edu). The four wwPDB partners operate a unified global software system that enforces community-agreed data standards and supports data Deposition, Biocuration, and Validation of ~11,000 new PDB entries annually (deposit.wwpdb.org). The RCSB PDB currently acts as the archive keeper, ensuring disaster recovery of PDB data and coordinating weekly updates. wwPDB partners disseminate the same archival data from multiple FTP sites, while operating complementary websites that provide their own views of PDB data with selected value-added information and links to related data resources. At present, the PDB archives experimental data, associated metadata, and 3D-atomic level structural models derived from three well-established methods: crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (3DEM). wwPDB partners are working closely with experts in related experimental areas (small-angle scattering, chemical cross-linking/mass spectrometry, Forster energy resonance transfer or FRET, etc.) to establish a federation of data resources that will support sustainable archiving and validation of 3D structural models and experimental data derived from integrative or hybrid methods.

  1. Life-Cycle Models for Survivable Systems

    National Research Council Canada - National Science Library

    Linger, Richard

    2002-01-01

    .... Current software development life-cycle models are not focused on creating survivable systems, and exhibit shortcomings when the goal is to develop systems with a high degree of assurance of survivability...

  2. Model Updating Nonlinear System Identification Toolbox Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ZONA Technology (ZONA) proposes to develop an enhanced model updating nonlinear system identification (MUNSID) methodology that utilizes flight data with...

  3. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

      In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular

  4. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

    In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular

  5. Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

    Czech Academy of Sciences Publication Activity Database

    Kissel, M.; Peschke, P.; Šubr, Vladimír; Ulbrich, Karel; Strunz, A. M.; Kühnlein, R.; Debus, J.; Friedrich, E.

    2002-01-01

    Roč. 29, č. 8 (2002), s. 1055-1062 ISSN 1619-7070 R&D Projects: GA ČR GV307/96/K226 Institutional research plan: CEZ:AV0Z4050913 Keywords : EPR effect * Radiolabelled macromolecules * Pharmacokinetic Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.568, year: 2002

  6. MMTF-An efficient file format for the transmission, visualization, and analysis of macromolecular structures.

    Directory of Open Access Journals (Sweden)

    Anthony R Bradley

    2017-06-01

    Full Text Available Recent advances in experimental techniques have led to a rapid growth in complexity, size, and number of macromolecular structures that are made available through the Protein Data Bank. This creates a challenge for macromolecular visualization and analysis. Macromolecular structure files, such as PDB or PDBx/mmCIF files can be slow to transfer, parse, and hard to incorporate into third-party software tools. Here, we present a new binary and compressed data representation, the MacroMolecular Transmission Format, MMTF, as well as software implementations in several languages that have been developed around it, which address these issues. We describe the new format and its APIs and demonstrate that it is several times faster to parse, and about a quarter of the file size of the current standard format, PDBx/mmCIF. As a consequence of the new data representation, it is now possible to visualize structures with millions of atoms in a web browser, keep the whole PDB archive in memory or parse it within few minutes on average computers, which opens up a new way of thinking how to design and implement efficient algorithms in structural bioinformatics. The PDB archive is available in MMTF file format through web services and data that are updated on a weekly basis.

  7. Isolation and chemical characterization of resistant macromolecular constituents in microalgae and marine sediments

    NARCIS (Netherlands)

    Gelin, F.

    1996-01-01

    The recognition of novel, insoluble and non-hydrolysable macromolecular constituents in protective tissues of fresh-water algae and higher plants has had a major impact on our understanding of the origin and fate of sedimentary organic matter (OM) in terrestrial and lacustrine deposits. The

  8. Generation dependent mesophase behavior in extended amphiphilic dendrons in the shape of macromolecular dumbbells.

    Science.gov (United States)

    Cho, Byoung-Ki; Jain, Anurag; Gruner, Sol M; Wiesner, Ulrich

    2005-04-28

    Small angle X-ray scattering studies of 2nd and 3rd generation based extended amphiphilic dendrons in the shape of macromolecular dumbbells with identical hydrophilic volume fractions suggest 2-D hexagonal columnar and Pm3n micellar cubic mesophases, respectively, elucidating the role of shape induced interface curvature in mesophase formation.

  9. An expert system for dispersion model interpretation

    International Nuclear Information System (INIS)

    Skyllingstad, E.D.; Ramsdell, J.V.

    1988-10-01

    A prototype expert system designed to diagnose dispersion model uncertainty is described in this paper with application to a puff transport model. The system obtains qualitative information from the model user and through an expert-derived knowledge base, performs a rating of the current simulation. These results can then be used in combination with dispersion model output for deciding appropriate evacuation measures. Ultimately, the goal of this work is to develop an expert system that may be operated accurately by an individual uneducated in meteorology or dispersion modeling. 5 refs., 3 figs

  10. Semantic models for adaptive interactive systems

    CERN Document Server

    Hussein, Tim; Lukosch, Stephan; Ziegler, Jürgen; Calvary, Gaëlle

    2013-01-01

    Providing insights into methodologies for designing adaptive systems based on semantic data, and introducing semantic models that can be used for building interactive systems, this book showcases many of the applications made possible by the use of semantic models.Ontologies may enhance the functional coverage of an interactive system as well as its visualization and interaction capabilities in various ways. Semantic models can also contribute to bridging gaps; for example, between user models, context-aware interfaces, and model-driven UI generation. There is considerable potential for using

  11. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    of the venous system require at least three elements: a resistor, a capacitor and an inductor, with the latter being of more importance in the venous than in the arterial system. Non-linearities must be considered in pressure/flow relations in the small venules, during venous collapse, or low flow conditions...

  12. Stochastic Models of Polymer Systems

    Science.gov (United States)

    2016-01-01

    published in non-peer-reviewed journals (N/A for none) The dynamics of stochastic gradient algorithms (submitted); Noisy Hegselmann- Krause Systems...algorithms for big data applications. (2) We studied stochastic dynamics of polymer systems in the mean field limit. (3) We studied noisy Hegselmann- Krause

  13. Switching model photovoltaic pumping system

    Science.gov (United States)

    Anis, Wagdy R.; Abdul-Sadek Nour, M.

    Photovoltaic (PV) pumping systems are widely used due to their simplicity, high reliability and low cost. A directly-coupled PV pumping system is the most reliable and least-cost PV system. The d.c. motor-pump group is not, however, working at its optimum operating point. A battery buffered PV pumping system introduces a battery between the PV array and the d.c. motor-pump group to ensure that the motor-pump group is operating at its optimum point. The size of the battery storage depends on system economics. If the battery is fully charged while solar radiation is available, the battery will discharge through the load while the PV array is disconnected. Hence, a power loss takes place. To overcome the above mentioned difficulty, a switched mode PV pumping is proposed. When solar radiation is available and the battery is fully charged, the battery is disconnected and the d.c. motor-pump group is directly coupled to the PV array. To avoid excessive operating voltage for the motor, a part of the PV array is switched off to reduce the voltage. As a result, the energy loss is significantly eliminated. Detailed analysis of the proposed system shows that the discharged water increases by about 10% when compared with a conventional battery-buffered system. The system transient performance just after the switching moment shows that the system returns to a steady state in short period. The variations in the system parameters lie within 1% of the rated values.

  14. Multiple system modelling of waste management

    International Nuclear Information System (INIS)

    Eriksson, Ola; Bisaillon, Mattias

    2011-01-01

    Highlights: → Linking of models will provide a more complete, correct and credible picture of the systems. → The linking procedure is easy to perform and also leads to activation of project partners. → The simulation procedure is a bit more complicated and calls for the ability to run both models. - Abstract: Due to increased environmental awareness, planning and performance of waste management has become more and more complex. Therefore waste management has early been subject to different types of modelling. Another field with long experience of modelling and systems perspective is energy systems. The two modelling traditions have developed side by side, but so far there are very few attempts to combine them. Waste management systems can be linked together with energy systems through incineration plants. The models for waste management can be modelled on a quite detailed level whereas surrounding systems are modelled in a more simplistic way. This is a problem, as previous studies have shown that assumptions on the surrounding system often tend to be important for the conclusions. In this paper it is shown how two models, one for the district heating system (MARTES) and another one for the waste management system (ORWARE), can be linked together. The strengths and weaknesses with model linking are discussed when compared to simplistic assumptions on effects in the energy and waste management systems. It is concluded that the linking of models will provide a more complete, correct and credible picture of the consequences of different simultaneous changes in the systems. The linking procedure is easy to perform and also leads to activation of project partners. However, the simulation procedure is a bit more complicated and calls for the ability to run both models.

  15. Modeling of power electronic systems with EMTP

    Science.gov (United States)

    Tam, Kwa-Sur; Dravid, Narayan V.

    1989-01-01

    In view of the potential impact of power electronics on power systems, there is need for a computer modeling/analysis tool to perform simulation studies on power systems with power electronic components as well as to educate engineering students about such systems. The modeling of the major power electronic components of the NASA Space Station Freedom Electric Power System is described along with ElectroMagnetic Transients Program (EMTP) and it is demonstrated that EMTP can serve as a very useful tool for teaching, design, analysis, and research in the area of power systems with power electronic components. EMTP modeling of power electronic circuits is described and simulation results are presented.

  16. System Level Modelling and Performance Estimation of Embedded Systems

    DEFF Research Database (Denmark)

    Tranberg-Hansen, Anders Sejer

    The advances seen in the semiconductor industry within the last decade have brought the possibility of integrating evermore functionality onto a single chip forming functionally highly advanced embedded systems. These integration possibilities also imply that as the design complexity increases, so...... an efficient system level design methodology, a modelling framework for performance estimation and design space exploration at the system level is required. This thesis presents a novel component based modelling framework for system level modelling and performance estimation of embedded systems. The framework...... is performed by having the framework produce detailed quantitative information about the system model under investigation. The project is part of the national Danish research project, Danish Network of Embedded Systems (DaNES), which is funded by the Danish National Advanced Technology Foundation. The project...

  17. Network model of security system

    Directory of Open Access Journals (Sweden)

    Adamczyk Piotr

    2016-01-01

    Full Text Available The article presents the concept of building a network security model and its application in the process of risk analysis. It indicates the possibility of a new definition of the role of the network models in the safety analysis. Special attention was paid to the development of the use of an algorithm describing the process of identifying the assets, vulnerability and threats in a given context. The aim of the article is to present how this algorithm reduced the complexity of the problem by eliminating from the base model these components that have no links with others component and as a result and it was possible to build a real network model corresponding to reality.

  18. Modeling Adaptive Behavior for Systems Design

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1994-01-01

    Field studies in modern work systems and analysis of recent major accidents have pointed to a need for better models of the adaptive behavior of individuals and organizations operating in a dynamic and highly competitive environment. The paper presents a discussion of some key characteristics...... of the predictive models required for the design of work supports systems, that is,information systems serving as the human-work interface. Three basic issues are in focus: 1.) Some fundamental problems in analysis and modeling modern dynamic work systems caused by the adaptive nature of human behavior; 2.......) The basic difference between the models of system functions used in engineering and design and those evolving from basic research within the various academic disciplines and finally 3.) The models and methods required for closed-loop, feedback system design....

  19. Model-based version management system framework

    International Nuclear Information System (INIS)

    Mehmood, W.

    2016-01-01

    In this paper we present a model-based version management system. Version Management System (VMS) a branch of software configuration management (SCM) aims to provide a controlling mechanism for evolution of software artifacts created during software development process. Controlling the evolution requires many activities to perform, such as, construction and creation of versions, identification of differences between versions, conflict detection and merging. Traditional VMS systems are file-based and consider software systems as a set of text files. File based VMS systems are not adequate for performing software configuration management activities such as, version control on software artifacts produced in earlier phases of the software life cycle. New challenges of model differencing, merge, and evolution control arise while using models as central artifact. The goal of this work is to present a generic framework model-based VMS which can be used to overcome the problem of tradition file-based VMS systems and provide model versioning services. (author)

  20. Very Large System Dynamics Models - Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Leonard Malczynski

    2008-10-01

    This paper provides lessons learned from developing several large system dynamics (SD) models. System dynamics modeling practice emphasize the need to keep models small so that they are manageable and understandable. This practice is generally reasonable and prudent; however, there are times that large SD models are necessary. This paper outlines two large SD projects that were done at two Department of Energy National Laboratories, the Idaho National Laboratory and Sandia National Laboratories. This paper summarizes the models and then discusses some of the valuable lessons learned during these two modeling efforts.

  1. Photochemical internalization of therapeutic macromolecular agents: a novel strategy to kill multidrug-resistant cancer cells.

    Science.gov (United States)

    Selbo, Pål K; Weyergang, Anette; Bonsted, Anette; Bown, Stephen G; Berg, Kristian

    2006-11-01

    Drug resistance is a major problem for chemotherapy. Entrapment of anticancer drugs in endolysosomal compartments or active extrusions by plasma membrane proteins of the ATP-binding cassette (ABC) superfamily are important resistance mechanisms. This study evaluated photochemical internalization (PCI) of membrane-impermeable macromolecules that are not the target of ABC drug pumps for treating multidrug-resistant (MDR) cancer cells. We used the drug-sensitive uterine fibrosarcoma cell line MES-SA and its MDR, P-glycoprotein (P-gp)-overexpressing derivative MES-SA/Dx5 with the photosensitizer disulfonated meso-tetraphenylporphine (TPPS(2a)) and broad spectrum illumination. The PCI of doxorubicin, the ribosome-inactivating protein gelonin and adenoviral transduction were assessed in both cell lines, together with the uptake and excretion of TPPS(2a) and of two fluid phase markers easily detectable by fluorescence [lucifer yellow (LY) and fluorescein isothiocyanate (FITC)-dextran], as a model of gelonin uptake. Both cell lines were resistant to PCI of doxorubicin, but equally sensitive to PCI of gelonin, even though the endocytosis rates of LY and FITC-dextran were significantly lower in the MDR cells. In control studies, MES-SA/Dx5 cells were more resistant to photodynamic therapy (TPPS(2a) + light only). This was not mediated by P-gp, as there were no differences in the uptake and efflux of TPPS(2a) between the cell lines. After adenoviral infection, PCI enhanced gene delivery in both cell lines. In conclusion, PCI of macromolecular therapeutic agents that are not targets of P-gp is a novel therapeutic strategy to kill MDR cancer cells.

  2. Test-driven modeling of embedded systems

    DEFF Research Database (Denmark)

    Munck, Allan; Madsen, Jan

    2015-01-01

    To benefit maximally from model-based systems engineering (MBSE) trustworthy high quality models are required. From the software disciplines it is known that test-driven development (TDD) can significantly increase the quality of the products. Using a test-driven approach with MBSE may have...... a similar positive effect on the quality of the system models and the resulting products and may therefore be desirable. To define a test-driven model-based systems engineering (TD-MBSE) approach, we must define this approach for numerous sub disciplines such as modeling of requirements, use cases......, scenarios, behavior, architecture, etc. In this paper we present a method that utilizes the formalism of timed automatons with formal and statistical model checking techniques to apply TD-MBSE to the modeling of system architecture and behavior. The results obtained from applying it to an industrial case...

  3. Precipitation-runoff modeling system; user's manual

    Science.gov (United States)

    Leavesley, G.H.; Lichty, R.W.; Troutman, B.M.; Saindon, L.G.

    1983-01-01

    The concepts, structure, theoretical development, and data requirements of the precipitation-runoff modeling system (PRMS) are described. The precipitation-runoff modeling system is a modular-design, deterministic, distributed-parameter modeling system developed to evaluate the impacts of various combinations of precipitation, climate, and land use on streamflow, sediment yields, and general basin hydrology. Basin response to normal and extreme rainfall and snowmelt can be simulated to evaluate changes in water balance relationships, flow regimes, flood peaks and volumes, soil-water relationships, sediment yields, and groundwater recharge. Parameter-optimization and sensitivity analysis capabilites are provided to fit selected model parameters and evaluate their individual and joint effects on model output. The modular design provides a flexible framework for continued model system enhancement and hydrologic modeling research and development. (Author 's abstract)

  4. An Empirical Model for Energy Storage Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rosewater, David Martin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Scott, Paul [TransPower, Poway, CA (United States)

    2016-03-17

    Improved models of energy storage systems are needed to enable the electric grid’s adaptation to increasing penetration of renewables. This paper develops a generic empirical model of energy storage system performance agnostic of type, chemistry, design or scale. Parameters for this model are calculated using test procedures adapted from the US DOE Protocol for Uniformly Measuring and Expressing the Performance of Energy Storage. We then assess the accuracy of this model for predicting the performance of the TransPower GridSaver – a 1 MW rated lithium-ion battery system that underwent laboratory experimentation and analysis. The developed model predicts a range of energy storage system performance based on the uncertainty of estimated model parameters. Finally, this model can be used to better understand the integration and coordination of energy storage on the electric grid.

  5. Brief History of Agricultural Systems Modeling

    Science.gov (United States)

    Jones, James W.; Antle, John M.; Basso, Bruno O.; Boote, Kenneth J.; Conant, Richard T.; Foster, Ian; Godfray, H. Charles J.; Herrrero, Mario; Howitt, Richard E.; Janssen, Sandor; hide

    2016-01-01

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the next generation models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of this history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. The lessons from history should be considered

  6. Methods for synthesizing the macromolecular constituents of smart nanosized carriers for controlled drug delivery.

    Science.gov (United States)

    Balaure, Paul Catalin; Grumezescu, Alexandru Mihai

    2014-01-01

    Smart multifunctional polymeric nanocarriers able to respond to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review deals with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional, much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index, as well as much more complex macromolecular architectures with strictly controlled chemical composition, such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/"living" free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described, highlighting their mechanistic details and their synthetic potential as well as their limitations. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers - the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with the therapeutic applications taking advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.

  7. Development of an online UV-visible microspectrophotometer for a macromolecular crystallography beamline.

    Science.gov (United States)

    Shimizu, Nobutaka; Shimizu, Tetsuya; Baba, Seiki; Hasegawa, Kazuya; Yamamoto, Masaki; Kumasaka, Takashi

    2013-11-01

    Measurement of the UV-visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV-visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury-xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

  8. The Temperature Optima and Temperature Sensitivity of Soil Respiration Explained By Macromolecular Rate Theory (MMRT).

    Science.gov (United States)

    Schipper, L. A.; O'Neill, T.; Arcus, V. L.

    2014-12-01

    One of the most fundamental factors controlling all biological and chemical processes is changing temperature. Temperature dependence was originally described by the Arrhenius function in the 19th century. This function provides an excellent description of chemical reaction rates. However, the Arrhenius function does not predict the temperature optimum of biological rates that is clearly evident in laboratory and field measurements. Previously, the temperature optimum of biological processes has been ascribed to denaturation of enzymes but the observed temperature optima in soil are often rather modest, occurring at about 40-50°C and generally less than recognised temperatures for protein unfolding. We have modified the Arrhenius function incorporating a temperature-dependent activation energy derived directly from first principles from thermodynamics of macromolecules. MacroMolecular Rate Theory (MMRT) accounts for large changes in the flexibility of enzymes during catalysis that result in changes in heat capacity (ΔC‡p) of the enzyme during the reaction. MMRT predicts an initially Arrhenius-like response followed by a temperature optimum without the need for enzyme denaturation (Hobbs et al., 2013. ACS Chemical Biology. 8: 2388-2393). Denaturation, of course, occurs at much higher temperatures. We have shown that MMRT fits biogeochemical data collected from laboratory and field studies with important implications for changes in absolute temperature sensitivity as temperature rises (Schipper et al., 2014. Global Change Biology). As the temperature optimum is approached the absolute temperature sensitivity of biological processes decreases to zero. Consequently, the absolute temperature-sensitivity of soil biological processes depends on both the change in ecosystem temperature and the temperature optimum of the biological process. MMRT also very clearly explains why Q10 values decline with increasing temperature more quickly than would be predicted from the

  9. Formal Modeling and Analysis of Timed Systems

    DEFF Research Database (Denmark)

    Larsen, Kim Guldstrand; Niebert, Peter

    This book constitutes the thoroughly refereed post-proceedings of the First International Workshop on Formal Modeling and Analysis of Timed Systems, FORMATS 2003, held in Marseille, France in September 2003. The 19 revised full papers presented together with an invited paper and the abstracts...... of two invited talks were carefully selected from 36 submissions during two rounds of reviewing and improvement. All current aspects of formal method for modeling and analyzing timed systems are addressed; among the timed systems dealt with are timed automata, timed Petri nets, max-plus algebras, real......-time systems, discrete time systems, timed languages, and real-time operating systems....

  10. Grey Box Modelling of Hydrological Systems

    DEFF Research Database (Denmark)

    Thordarson, Fannar Ørn

    The main topic of the thesis is grey box modelling of hydrologic systems, as well as formulation and assessment of their embedded uncertainties. Grey box model is a combination of a white box model, a physically-based model that is traditionally formulated using deterministic ordinary differential...... the lack of fit in state space formulation, and further support decisions for a model expansion. By using stochastic differential equations to formulate the dynamics of the hydrological system, either the complexity of the model can be increased by including the necessary hydrological processes...... in the model, or formulation of process noise can be considered so that it meets the physical limits of the hydrological system and give an adequate description of the embedded uncertainty in model structure. The thesis consists of two parts: a summary report and a part which contains six scientific papers...

  11. Sample preparation of biological macromolecular assemblies for the determination of high-resolution structures by cryo-electron microscopy.

    Science.gov (United States)

    Stark, Holger; Chari, Ashwin

    2016-02-01

    Single particle cryo-EM has recently developed into a powerful tool to determine the 3D structure of macromolecular complexes at near-atomic resolution, which allows structural biologists to build atomic models of proteins. All technical aspects of cryo-EM technology have been considerably improved over the last two decades, including electron microscopic hardware, image processing software and the ever growing speed of computers. This leads to a more widespread use of the technique, and it can be anticipated that further automation of electron microscopes and image processing tools will soon fully shift the focus away from the technological aspects, onto biological questions that can be answered. In single particle cryo-EM, no crystals of a macromolecule are required. In contrast to X-ray crystallography, this significantly facilitates structure determination by cryo-EM. Nevertheless, a relatively high level of biochemical control is still essential to obtain high-resolution structures by cryo-EM, and it can be anticipated that the success of the cryo-EM technology goes hand in hand with further developments of sample purification and preparation techniques. This will allow routine high-resolution structure determination of the many macromolecular complexes of the cell that until now represent evasive targets for X-ray crystallographers. Here we discuss the various biochemical tools that are currently available and the existing sample purification and preparation techniques for cryo-EM grid preparation that are needed to obtain high-resolution images for structure determination. © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. The Guided System Development Framework: Modeling and Verifying Communication Systems

    DEFF Research Database (Denmark)

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.; Nielson, Flemming

    2014-01-01

    . The Guided System Development framework contributes to more secure communication systems by aiding the development of such systems. The framework features a simple modelling language, step-wise refinement from models to implementation, interfaces to security verification tools, and code generation from...... the verified specification. The refinement process carries thus security properties from the model to the implementation. Our approach also supports verification of systems previously developed and deployed. Internally, the reasoning in our framework is based on the Beliefs and Knowledge tool, a verification...

  13. System Advisor Model: Flat Plate Photovoltaic Performance Modeling Validation Report

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Janine [National Renewable Energy Lab. (NREL), Golden, CO (United States); Whitmore, Jonathan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kaffine, Leah [National Renewable Energy Lab. (NREL), Golden, CO (United States); Blair, Nate [National Renewable Energy Lab. (NREL), Golden, CO (United States); Dobos, Aron P. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2013-12-01

    The System Advisor Model (SAM) is a free software tool that performs detailed analysis of both system performance and system financing for a variety of renewable energy technologies. This report provides detailed validation of the SAM flat plate photovoltaic performance model by comparing SAM-modeled PV system generation data to actual measured production data for nine PV systems ranging from 75 kW to greater than 25 MW in size. The results show strong agreement between SAM predictions and field data, with annualized prediction error below 3% for all fixed tilt cases and below 8% for all one axis tracked cases. The analysis concludes that snow cover and system outages are the primary sources of disagreement, and other deviations resulting from seasonal biases in the irradiation models and one axis tracking issues are discussed in detail.

  14. Coupling population dynamics with earth system models: the POPEM model.

    Science.gov (United States)

    Navarro, Andrés; Moreno, Raúl; Jiménez-Alcázar, Alfonso; Tapiador, Francisco J

    2017-09-16

    Precise modeling of CO 2 emissions is important for environmental research. This paper presents a new model of human population dynamics that can be embedded into ESMs (Earth System Models) to improve climate modeling. Through a system dynamics approach, we develop a cohort-component model that successfully simulates historical population dynamics with fine spatial resolution (about 1°×1°). The population projections are used to improve the estimates of CO 2 emissions, thus transcending the bulk approach of existing models and allowing more realistic non-linear effects to feature in the simulations. The module, dubbed POPEM (from Population Parameterization for Earth Models), is compared with current emission inventories and validated against UN aggregated data. Finally, it is shown that the module can be used to advance toward fully coupling the social and natural components of the Earth system, an emerging research path for environmental science and pollution research.

  15. Spinal Cord Injury Model System Information Network

    Science.gov (United States)

    ... the UAB-SCIMS Contact the UAB-SCIMS UAB Spinal Cord Injury Model System Newly Injured Health Daily Living Consumer ... Information Network The University of Alabama at Birmingham Spinal Cord Injury Model System (UAB-SCIMS) maintains this Information Network ...

  16. Statistical Model Checking for Stochastic Hybrid Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Du, Dehui; Larsen, Kim Guldstrand

    2012-01-01

    This paper presents novel extensions and applications of the UPPAAL-SMC model checker. The extensions allow for statistical model checking of stochastic hybrid systems. We show how our race-based stochastic semantics extends to networks of hybrid systems, and indicate the integration technique ap...

  17. Systemic, Ecological Model for Rehabilitation Counseling.

    Science.gov (United States)

    Hershenson, David B.

    1998-01-01

    Presents a reformulation of Hershenson's theoretical model for rehabilitation counseling in systemic and ecological terms. This macrosystem is organized by precipitating event of disability and is composed of four systems: consumer, functional, provider, and contextual. Discusses the use of the model for selecting rehabilitation interventions…

  18. Modeling complex work systems - method meets reality

    NARCIS (Netherlands)

    van der Veer, Gerrit C.; Hoeve, Machteld; Lenting, Bert

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the

  19. System dynamics modelling of situation awareness

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2015-11-01

    Full Text Available . The feedback loops and delays in the Command and Control system also contribute to the complex dynamic behavior. This paper will build on existing situation awareness models to develop a System Dynamics model to support a qualitative investigation through...

  20. Dynamic modeling of the INAPRO aquaponic system

    NARCIS (Netherlands)

    Karimanzira, Divas; Keesman, Karel J.; Kloas, Werner; Baganz, Daniela; Rauschenbach, Thomas

    2016-01-01

    The use of modeling techniques to analyze aquaponics systems is demonstrated with an example of dynamic modeling for the production of Nile tilapia (Oreochromis niloticus) and tomatoes (Solanum lycopersicon) using the innovative double recirculating aquaponic system ASTAF-PRO. For the management

  1. Formal heterogeneous system modeling with SystemC

    DEFF Research Database (Denmark)

    Niaki, Seyed Hosein Attarzadeh; Jakobsen, Mikkel Koefoed; Sulonen, Tero

    2012-01-01

    Electronic System Level (ESL) design of embedded systems proposes raising the abstraction level of the design entry to cope with the increasing complexity of such systems. To exploit the benefits of ESL, design languages should allow specification of models which are a) heterogeneous, to describe...... to focus on specifying the pure functional aspects. A key advantage is that the formalism is used to export the structure and behavior of the models via introspection as an abstract representation for further analysis and synthesis....

  2. Regression Models for Repairable Systems

    Czech Academy of Sciences Publication Activity Database

    Novák, Petr

    2015-01-01

    Roč. 17, č. 4 (2015), s. 963-972 ISSN 1387-5841 Institutional support: RVO:67985556 Keywords : Reliability analysis * Repair models * Regression Subject RIV: BB - Applied Statistics , Operational Research Impact factor: 0.782, year: 2015 http://library.utia.cas.cz/separaty/2015/SI/novak-0450902.pdf

  3. Mathematical Modeling Of Life-Support Systems

    Science.gov (United States)

    Seshan, Panchalam K.; Ganapathi, Balasubramanian; Jan, Darrell L.; Ferrall, Joseph F.; Rohatgi, Naresh K.

    1994-01-01

    Generic hierarchical model of life-support system developed to facilitate comparisons of options in design of system. Model represents combinations of interdependent subsystems supporting microbes, plants, fish, and land animals (including humans). Generic model enables rapid configuration of variety of specific life support component models for tradeoff studies culminating in single system design. Enables rapid evaluation of effects of substituting alternate technologies and even entire groups of technologies and subsystems. Used to synthesize and analyze life-support systems ranging from relatively simple, nonregenerative units like aquariums to complex closed-loop systems aboard submarines or spacecraft. Model, called Generic Modular Flow Schematic (GMFS), coded in such chemical-process-simulation languages as Aspen Plus and expressed as three-dimensional spreadsheet.

  4. Systematic modelling and simulation of refrigeration systems

    DEFF Research Database (Denmark)

    Rasmussen, Bjarne D.; Jakobsen, Arne

    1998-01-01

    The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose of the s......The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose...... of the simulation, to select appropriate component models and to set up the equations in a well-arranged way. In this paper the outline of such a method is proposed and examples showing the use of this method for simulation of refrigeration systems are given....

  5. Modeling and analysis of stochastic systems

    CERN Document Server

    Kulkarni, Vidyadhar G

    2011-01-01

    Based on the author's more than 25 years of teaching experience, Modeling and Analysis of Stochastic Systems, Second Edition covers the most important classes of stochastic processes used in the modeling of diverse systems, from supply chains and inventory systems to genetics and biological systems. For each class of stochastic process, the text includes its definition, characterization, applications, transient and limiting behavior, first passage times, and cost/reward models. Along with reorganizing the material, this edition revises and adds new exercises and examples. New to the second edi

  6. Formal heterogeneous system modeling with SystemC

    DEFF Research Database (Denmark)

    Niaki, Seyed Hosein Attarzadeh; Jakobsen, Mikkel Koefoed; Sulonen, Tero

    2012-01-01

    Electronic System Level (ESL) design of embedded systems proposes raising the abstraction level of the design entry to cope with the increasing complexity of such systems. To exploit the benefits of ESL, design languages should allow specification of models which are a) heterogeneous, to describe...

  7. Systems Engineering Model for ART Energy Conversion

    Energy Technology Data Exchange (ETDEWEB)

    Mendez Cruz, Carmen Margarita [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rochau, Gary E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wilson, Mollye C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    The near-term objective of the EC team is to establish an operating, commercially scalable Recompression Closed Brayton Cycle (RCBC) to be constructed for the NE - STEP demonstration system (demo) with the lowest risk possible. A systems engineering approach is recommended to ensure adequate requirements gathering, documentation, and mode ling that supports technology development relevant to advanced reactors while supporting crosscut interests in potential applications. A holistic systems engineering model was designed for the ART Energy Conversion program by leveraging Concurrent Engineering, Balance Model, Simplified V Model, and Project Management principles. The resulting model supports the identification and validation of lifecycle Brayton systems requirements, and allows designers to detail system-specific components relevant to the current stage in the lifecycle, while maintaining a holistic view of all system elements.

  8. Modeling aluminum-air battery systems

    Science.gov (United States)

    Savinell, R. F.; Willis, M. S.

    The performance of a complete aluminum-air battery system was studied with a flowsheet model built from unit models of each battery system component. A plug flow model for heat transfer was used to estimate the amount of heat transferred from the electrolyte to the air stream. The effect of shunt currents on battery performance was found to be insignificant. Using the flowsheet simulator to analyze a 100 cell battery system now under development demonstrated that load current, aluminate concentration, and electrolyte temperature are dominant variables controlling system performance. System efficiency was found to decrease as both load current and aluminate concentration increases. The flowsheet model illustrates the interdependence of separate units on overall system performance.

  9. Model-Based Design for Embedded Systems

    CERN Document Server

    Nicolescu, Gabriela

    2009-01-01

    Model-based design allows teams to start the design process from a high-level model that is gradually refined through abstraction levels to ultimately yield a prototype. This book describes the main facets of heterogeneous system design. It focuses on multi-core methodological issues, real-time analysis, and modeling and validation

  10. Critically Important Object Security System Element Model

    Directory of Open Access Journals (Sweden)

    I. V. Khomyackov

    2012-03-01

    Full Text Available A stochastic model of critically important object security system element has been developed. The model includes mathematical description of the security system element properties and external influences. The state evolution of the security system element is described by the semi-Markov process with finite states number, the semi-Markov matrix and the initial semi-Markov process states probabilities distribution. External influences are set with the intensity of the Poisson thread.

  11. A model for international border management systems.

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, Ruth Ann

    2008-09-01

    To effectively manage the security or control of its borders, a country must understand its border management activities as a system. Using its systems engineering and security foundations as a Department of Energy National Security Laboratory, Sandia National Laboratories has developed such an approach to modeling and analyzing border management systems. This paper describes the basic model and its elements developed under Laboratory Directed Research and Development project 08-684.

  12. A strategic review of electricity systems models

    International Nuclear Information System (INIS)

    Foley, A.M.; O Gallachoir, B.P.; McKeogh, E.J.; Hur, J.; Baldick, R.

    2010-01-01

    Electricity systems models are software tools used to manage electricity demand and the electricity systems, to trade electricity and for generation expansion planning purposes. Various portfolios and scenarios are modelled in order to compare the effects of decision making in policy and on business development plans in electricity systems so as to best advise governments and industry on the least cost economic and environmental approach to electricity supply, while maintaining a secure supply of sufficient quality electricity. The modelling techniques developed to study vertically integrated state monopolies are now applied in liberalised markets where the issues and constraints are more complex. This paper reviews the changing role of electricity systems modelling in a strategic manner, focussing on the modelling response to key developments, the move away from monopoly towards liberalised market regimes and the increasing complexity brought about by policy targets for renewable energy and emissions. The paper provides an overview of electricity systems modelling techniques, discusses a number of key proprietary electricity systems models used in the USA and Europe and provides an information resource to the electricity analyst not currently readily available in the literature on the choice of model to investigate different aspects of the electricity system. (author)

  13. Human performance modeling for system of systems analytics.

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E. (INTERA, Inc., Austin, TX); Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  14. Reliability models for Space Station power system

    Science.gov (United States)

    Singh, C.; Patton, A. D.; Kim, Y.; Wagner, H.

    1987-01-01

    This paper presents a methodology for the reliability evaluation of Space Station power system. The two options considered are the photovoltaic system and the solar dynamic system. Reliability models for both of these options are described along with the methodology for calculating the reliability indices.

  15. System identification application using Hammerstein model

    Indian Academy of Sciences (India)

    Saban Ozer

    because of its advanced theoretical background [3–5, 10]. However, many systems in real life have nonlinear beha- ... To describe a polynomial non-linear system with memory, the Volterra series expansion has been the ... suppression and adaptive noise suppression [19]. 2.3 Hammerstein model. Many systems can be ...

  16. Using Interaction Scenarios to Model Information Systems

    DEFF Research Database (Denmark)

    Bækgaard, Lars; Bøgh Andersen, Peter

    The purpose of this paper is to define and discuss a set of interaction primitives that can be used to model the dynamics of socio-technical activity systems, including information systems, in a way that emphasizes structural aspects of the interaction that occurs in such systems. The primitives...

  17. Model Validation for Simulations of Vehicle Systems

    Science.gov (United States)

    2012-08-01

    jackknife”, Annals of Statistics, 7:1-26, 1979. [45] B. Efron and G. Gong, “A leisurely look at the bootstrap, the jackknife, and cross-validation”, The...battery model developed in the Automotive Research Center, a US Army Center of Excellence for modeling and simulation of ground vehicle systems...Sandia National Laboratories and a battery model developed in the Automotive Research Center, a US Army Center of Excellence for modeling and simulation

  18. Models of cuspy triaxial stellar systems. IV: Rotating systems

    OpenAIRE

    Carpintero, D. D.; Muzzio, J. C.

    2016-01-01

    We built two self-consistent models of triaxial, cuspy, rotating stellar systems adding rotation to non-rotating models presented in previous papers of this series. The final angular velocity of the material is not constant and varies with the distance to the center and with the height over the equator of the systems, but the figure rotation is very uniform in both cases. Even though the addition of rotation to the models modifies their original semiaxes ratios, the final rotating models are ...

  19. Spatial Models and Networks of Living Systems

    DEFF Research Database (Denmark)

    Juul, Jeppe Søgaard

    with interactions defined by network topology. In this thesis I first describe three different biological models of ageing and cancer, in which spatial structure is important for the system dynamics. I then turn to describe characteristics of ecosystems consisting of three cyclically interacting species......When studying the dynamics of living systems, insight can often be gained by developing a mathematical model that can predict future behaviour of the system or help classify system characteristics. However, in living cells, organisms, and especially groups of interacting individuals, a large number...... of different factors influence the time development of the system. This often makes it challenging to construct a mathematical model from which to draw conclusions. One traditional way of capturing the dynamics in a mathematical model is to formulate a set of coupled differential equations for the essential...

  20. Mechatronic Systems Design Methods, Models, Concepts

    CERN Document Server

    Janschek, Klaus

    2012-01-01

    In this textbook, fundamental methods for model-based design of mechatronic systems are presented in a systematic, comprehensive form. The method framework presented here comprises domain-neutral methods for modeling and performance analysis: multi-domain modeling (energy/port/signal-based), simulation (ODE/DAE/hybrid systems), robust control methods, stochastic dynamic analysis, and quantitative evaluation of designs using system budgets. The model framework is composed of analytical dynamic models for important physical and technical domains of realization of mechatronic functions, such as multibody dynamics, digital information processing and electromechanical transducers. Building on the modeling concept of a technology-independent generic mechatronic transducer, concrete formulations for electrostatic, piezoelectric, electromagnetic, and electrodynamic transducers are presented. More than 50 fully worked out design examples clearly illustrate these methods and concepts and enable independent study of th...

  1. FSM Model of a Simple Photovoltaic System

    Directory of Open Access Journals (Sweden)

    Martina Latkova

    2015-01-01

    Full Text Available The paper describes a simulation model of a simple photovoltaic system intended as a tool for testing the use of finite state machines for simulations representing a long-term operation of renewable energy sources. The mathematical model of the photovoltaic system is described first. Then it is used to build a finite state machine model that calculates a power output of the photovoltaic system for changing values of a solar irradiance and a temperature. Data measured on a real photovoltaic installation are used to verify model’s accuracy through its comparison with a previously created and verified Matlab model. The finite state machine model presented in this paper was created using Ptolemy II software.

  2. Structural system identification: Structural dynamics model validation

    Energy Technology Data Exchange (ETDEWEB)

    Red-Horse, J.R.

    1997-04-01

    Structural system identification is concerned with the development of systematic procedures and tools for developing predictive analytical models based on a physical structure`s dynamic response characteristics. It is a multidisciplinary process that involves the ability (1) to define high fidelity physics-based analysis models, (2) to acquire accurate test-derived information for physical specimens using diagnostic experiments, (3) to validate the numerical simulation model by reconciling differences that inevitably exist between the analysis model and the experimental data, and (4) to quantify uncertainties in the final system models and subsequent numerical simulations. The goal of this project was to develop structural system identification techniques and software suitable for both research and production applications in code and model validation.

  3. Macromolecular Engineering: New Routes Towards the Synthesis of Well-??Defined Polyethers/Polyesters Co/Terpolymers with Different Architectures

    KAUST Repository

    Alamri, Haleema

    2016-05-18

    The primary objective of this research was to develop a new and efficient pathway for well-defined multicomponent homo/co/terpolymers of cyclic esters/ethers using an organocatalytic approach with an emphasis on the macromolecular engineering aspects of the overall synthesis. Macromolecular engineering (as discussed in the first chapter) of homo/copolymers refers to the specific tailoring of these materials for achieving an easy and reproducible synthesis that results in precise molecular characteristics, i.e. molecular weight and polydispersity, as well as specific structure and end?group choices. Precise control of these molecular characteristics will provide access to new materials that can be used for pre-targeted purposes such as biomedical applications. Among the most commonly used engineering materials are polyesters (biocompatible and biodegradable) and polyethers (biocompatible), either as homopolymers or when or copolymers with linear structures. The ability to create non-linear structures, for example stars, will open new horizons in the applications of these important polymeric materials. The second part of this thesis describes the synthesis of aliphatic polyesters, particularly polycaprolactone and polylactide, using a metal-free initiator/catalyst system. A phosphazene base (t?BuP2) was used as the catalyst for the ring-opening copolymerization of ?-aprolactone (??CL) and L,Lactide (LLA) at room temperature with a variety of protic initiators in different solvents. These studies provided important information for the design of a metal-free route toward the synthesis of polyester?based (bio) materials. The third part of the thesis describes a novel route for the one?pot synthesis of polyether-b polyester block copolymers with either a linear or a specific macromolecular architecture. Poly (styrene oxide)?b?poly(caprolactone)?b?poly(L,lactide) was prepared using this method with the goal of synthesizing poly(styrene oxide)-based materials since this

  4. A MICROCOMPUTER MODEL FOR IRRIGATION SYSTEM EVALUATION

    OpenAIRE

    Williams, Jeffery R.; Buller, Orlan H.; Dvorak, Gary J.; Manges, Harry L.

    1988-01-01

    ICEASE (Irrigation Cost Estimator and System Evaluator) is a microcomputer model designed and developed to meet the need for conducting economic evaluation of adjustments to irrigation systems and management techniques to improve the use of irrigated water. ICEASE can calculate the annual operating costs for irrigation systems and has five options that can be used to economically evaluate improvements in the pumping plant or the way the irrigation system is used for crop production.

  5. MODEL DRIVEN DEVELOPMENT OF ONLINE BANKING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Bresfelean Vasile Paul

    2011-07-01

    Full Text Available In case of online applications the cycle of software development varies from the routine. The online environment, the variety of users, the treatability of the mass of information created by them, the reusability and the accessibility from different devices are all factors of these systems complexity. The use of model drive approach brings several advantages that ease up the development process. Working prototypes that simplify client relationship and serve as the base of model tests can be easily made from models describing the system. These systems make possible for the banks clients to make their desired actions from anywhere. The user has the possibility of accessing information or making transactions.

  6. Modelling and parameter estimation of dynamic systems

    CERN Document Server

    Raol, JR; Singh, J

    2004-01-01

    Parameter estimation is the process of using observations from a system to develop mathematical models that adequately represent the system dynamics. The assumed model consists of a finite set of parameters, the values of which are calculated using estimation techniques. Most of the techniques that exist are based on least-square minimization of error between the model response and actual system response. However, with the proliferation of high speed digital computers, elegant and innovative techniques like filter error method, H-infinity and Artificial Neural Networks are finding more and mor

  7. System Model of Daily Sediment Yield

    Science.gov (United States)

    Sharma, T. C.; Dickinson, W. T.

    1980-06-01

    Input-output systems concepts have been applied to the modeling of daily runoff-sediment yield of the Thames River in southern Ontario, Canada. Spectral and correlation techniques have been used to construct a parsimonious model of daily sediment yields. It is shown that a linear discrete dynamic model is possible in terms of the log-transformed daily runoff and sediment yield sequences. The fluvial system of the Thames River watershed exhibits a weak memory on a daily basis, and the noise component corrupting the watershed fluvial system resembles a white noise process.

  8. Externalizing Behaviour for Analysing System Models

    DEFF Research Database (Denmark)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, René Rydhof

    2013-01-01

    System models have recently been introduced to model organisations and evaluate their vulnerability to threats and especially insider threats. Especially for the latter these models are very suitable, since insiders can be assumed to have more knowledge about the attacked organisation than outside......, if not impossible task to change behaviours. Especially when considering social engineering or the human factor in general, the ability to use different kinds of behaviours is essential. In this work we present an approach to make the behaviour a separate component in system models, and explore how to integrate...

  9. Model transformation based information system modernization

    Directory of Open Access Journals (Sweden)

    Olegas Vasilecas

    2013-03-01

    Full Text Available Information systems begin to date increasingly faster because of rapidly changing business environment. Usually, small changes are not sufficient to adapt complex legacy information systems to changing business needs. A new functionality should be installed with the requirement of putting business data in the smallest possible risk. Information systems modernization problems are beeing analyzed in this paper and a method for information system modernization is proposed. It involves programming code transformation into abstract syntax tree metamodel (ASTM and model based transformation from ASTM into knowledge discovery model (KDM. The method is validated on example for SQL language.

  10. Macromolecular structures for boron neutron-capture therapy

    International Nuclear Information System (INIS)

    Kne, R.R.; Hawthorne, M.F.

    1995-01-01

    A general synthetic method has been developed for the rapid and efficient production of a variety of boron-rich macromolecules suitable for conjugation with or inclusion in receptor-mediated delivery systems as well as other delivery systems. Preparation techniques have been developed to yield precisely ordered oligophosphates which are soluble, hydrophilic, may be homogeneous, and may be prepared with a variety of functional groups. (author)

  11. Photovoltaic System Modeling. Uncertainty and Sensitivity Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Clifford W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martin, Curtis E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    We report an uncertainty and sensitivity analysis for modeling AC energy from ph otovoltaic systems . Output from a PV system is predicted by a sequence of models. We quantify u ncertainty i n the output of each model using empirical distribution s of each model's residuals. We propagate uncertainty through the sequence of models by sampli ng these distributions to obtain a n empirical distribution of a PV system's output. We consider models that: (1) translate measured global horizontal, direct and global diffuse irradiance to plane - of - array irradiance; (2) estimate effective irradiance; (3) predict cell temperature; (4) estimate DC voltage, current and power ; (5) reduce DC power for losses due to inefficient maximum power point tracking or mismatch among modules; and (6) convert DC to AC power . O ur analysis consider s a notional PV system com prising an array of FirstSolar FS - 387 modules and a 250 kW AC inverter ; we use measured irradiance and weather at Albuquerque, NM. We found the uncertainty in PV syste m output to be relatively small, on the order of 1% for daily energy. We found that unce rtainty in the models for POA irradiance and effective irradiance to be the dominant contributors to uncertainty in predicted daily energy. Our analysis indicates that efforts to reduce the uncertainty in PV system output predictions may yield the greatest improvements by focusing on the POA and effective irradiance models.

  12. Climate Model Diagnostic Analyzer Web Service System

    Science.gov (United States)

    Lee, S.; Pan, L.; Zhai, C.; Tang, B.; Kubar, T. L.; Li, J.; Zhang, J.; Wang, W.

    2015-12-01

    Both the National Research Council Decadal Survey and the latest Intergovernmental Panel on Climate Change Assessment Report stressed the need for the comprehensive and innovative evaluation of climate models with the synergistic use of global satellite observations in order to improve our weather and climate simulation and prediction capabilities. The abundance of satellite observations for fundamental climate parameters and the availability of coordinated model outputs from CMIP5 for the same parameters offer a great opportunity to understand and diagnose model biases in climate models. In addition, the Obs4MIPs efforts have created several key global observational datasets that are readily usable for model evaluations. However, a model diagnostic evaluation process requires physics-based multi-variable comparisons that typically involve large-volume and heterogeneous datasets, making them both computationally- and data-intensive. In response, we have developed a novel methodology to diagnose model biases in contemporary climate models and implementing the methodology as a web-service based, cloud-enabled, provenance-supported climate-model evaluation system. The evaluation system is named Climate Model Diagnostic Analyzer (CMDA), which is the product of the research and technology development investments of several current and past NASA ROSES programs. The current technologies and infrastructure of CMDA are designed and selected to address several technical challenges that the Earth science modeling and model analysis community faces in evaluating and diagnosing climate models. In particular, we have three key technology components: (1) diagnostic analysis methodology; (2) web-service based, cloud-enabled technology; (3) provenance-supported technology. The diagnostic analysis methodology includes random forest feature importance ranking, conditional probability distribution function, conditional sampling, and time-lagged correlation map. We have implemented the

  13. Transforming Graphical System Models to Graphical Attack Models

    DEFF Research Database (Denmark)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, Rene Rydhof

    2016-01-01

    Manually identifying possible attacks on an organisation is a complex undertaking; many different factors must be considered, and the resulting attack scenarios can be complex and hard to maintain as the organisation changes. System models provide a systematic representation of organisations...... that helps in structuring attack identification and can integrate physical, virtual, and social components. These models form a solid basis for guiding the manual identification of attack scenarios. Their main benefit, however, is in the analytic generation of attacks. In this work we present a systematic...... approach to transforming graphical system models to graphical attack models in the form of attack trees. Based on an asset in the model, our transformations result in an attack tree that represents attacks by all possible actors in the model, after which the actor in question has obtained the asset....

  14. CTBT integrated verification system evaluation model supplement

    Energy Technology Data Exchange (ETDEWEB)

    EDENBURN,MICHAEL W.; BUNTING,MARCUS; PAYNE JR.,ARTHUR C.; TROST,LAWRENCE C.

    2000-03-02

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia's Monitoring Systems and Technology Center and has been funded by the U.S. Department of Energy's Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, ''top-level,'' modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM's unique features is that it integrates results from the various CTBT sensor technologies (seismic, in sound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection), location accuracy, and identification capability of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system's performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. The original IVSEM report, CTBT Integrated Verification System Evaluation Model, SAND97-25 18, described version 1.2 of IVSEM. This report describes the changes made to IVSEM version 1.2 and the addition of identification capability estimates that have been incorporated into IVSEM version 2.0.

  15. CTBT integrated verification system evaluation model supplement

    International Nuclear Information System (INIS)

    EDENBURN, MICHAEL W.; BUNTING, MARCUS; PAYNE, ARTHUR C. JR.; TROST, LAWRENCE C.

    2000-01-01

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia's Monitoring Systems and Technology Center and has been funded by the U.S. Department of Energy's Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, ''top-level,'' modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM's unique features is that it integrates results from the various CTBT sensor technologies (seismic, in sound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection), location accuracy, and identification capability of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system's performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. The original IVSEM report, CTBT Integrated Verification System Evaluation Model, SAND97-25 18, described version 1.2 of IVSEM. This report describes the changes made to IVSEM version 1.2 and the addition of identification capability estimates that have been incorporated into IVSEM version 2.0

  16. A distributed snow-evolution modeling system (SnowModel)

    Science.gov (United States)

    Glen E. Liston; Kelly. Elder

    2006-01-01

    SnowModel is a spatially distributed snow-evolution modeling system designed for application in landscapes, climates, and conditions where snow occurs. It is an aggregation of four submodels: MicroMet defines meteorological forcing conditions, EnBal calculates surface energy exchanges, SnowPack simulates snow depth and water-equivalent evolution, and SnowTran-3D...

  17. Local analysis of strains and rotations for macromolecular electron microscopy maps

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Ramos, A.; Prieto, F.; Melero, R.; Martin-Benito, J.; Jonic, S.; Navas-Calvente, J.; Vargas, J.; Oton, J.; Abrishami, V.; Rosa-Trevin, J.L. de la; Gomez-Blanco, J.; Vilas, J.L.; Marabini, R.; Carazo, R.; Sorzano, C.O.S.

    2016-07-01

    Macromolecular complexes can be considered as molecular nano-machines that must have mobile parts in order to perform their physiological functions. The reordering of their parts is essential to execute their task. These rearrangements induce local strains and rotations which, after analyzing them, may provide relevant information about how the proteins perform their function. In this project these deformations of the macromolecular complexes are characterized, translating into a “mathematical language” the conformational changes of the complexes when they perform their function. Electron Microscopy (EM) volumes are analyzed using a method that uses B-splines as its basis functions. It is shown that the results obtained are consistent with the conformational changes described in their corresponding reference publications. (Author)

  18. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    International Nuclear Information System (INIS)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

    2013-01-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein

  19. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Aller, Pierre [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Alguel, Yilmaz; Cameron, Alex [Imperial College, London SW7 2AZ (United Kingdom); Axford, Danny; Owen, Robin L. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Armour, Wes [Oxford e-Research Centre (OeRC), Keble Road, Oxford OX1 3QG (United Kingdom); Waterman, David G. [Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0FA (United Kingdom); Iwata, So [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2013-08-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  20. From “Simple” DNA-Protein Interactions to the Macromolecular Machines of Gene Expression

    Science.gov (United States)

    von Hippel, Peter H.

    2008-01-01

    The physicochemical concepts that underlie our present ideas on the structure and assembly of the “macromolecular machines of gene expression” are developed, starting with the structure and folding of the individual protein and DNA components, the thermodynamics and kinetics of their conformational rearrangements during complex assembly, and the molecular basis of the sequence specificity and recognition interactions of the final assemblies that include the DNA genome. The role of diffusion in reduced dimensions in the kinetics of the assembly of macromolecular machines from their components is also considered, and diffusion-driven reactions are compared with those fueled by ATP binding and hydrolysis, as well as by the specific covalent chemical modifications involved in rearranging chromatin and modifying signal transduction networks in higher organisms. PMID:17477836

  1. From "simple" DNA-protein interactions to the macromolecular machines of gene expression.

    Science.gov (United States)

    von Hippel, Peter H

    2007-01-01

    The physicochemical concepts that underlie our present ideas on the structure and assembly of the "macromolecular machines of gene expression" are developed, starting with the structure and folding of the individual protein and DNA components, the thermodynamics and kinetics of their conformational rearrangements during complex assembly, and the molecular basis of the sequence specificity and recognition interactions of the final assemblies that include the DNA genome. The role of diffusion in reduced dimensions in the kinetics of the assembly of macromolecular machines from their components is also considered, and diffusion-driven reactions are compared with those fueled by ATP binding and hydrolysis, as well as by the specific covalent chemical modifications involved in rearranging chromatin and modifying signal transduction networks in higher organisms.

  2. Long-Wavelength X-Ray Diffraction and Its Applications in Macromolecular Crystallography.

    Science.gov (United States)

    Weiss, Manfred S

    2017-01-01

    For many years, diffraction experiments in macromolecular crystallography at X-ray wavelengths longer than that of Cu-K α (1.54 Å) have been largely underappreciated. Effects caused by increased X-ray absorption result in the fact that these experiments are more difficult than the standard diffraction experiments at short wavelengths. However, due to the also increased anomalous scattering of many biologically relevant atoms, important additional structural information can be obtained. This information, in turn, can be used for phase determination, for substructure identification, in molecular replacement approaches, as well as in structure refinement. This chapter reviews the possibilities and the difficulties associated with such experiments, and it provides a short description of two macromolecular crystallography synchrotron beam lines dedicated to long-wavelength X-ray diffraction experiments.

  3. Romp: The Method of Choice for Precise Macromolecular Engineering and Synthesis of Smart Materials

    Science.gov (United States)

    Khosravi, Ezat; Castle, Thomas C.; Kujawa, Margaret; Leejarkpai, Jan; Hutchings, Lian R.; Hine, Peter J.

    The recent advances in olefin metathesis highlight the impact of Ring Opening Metathesis Polymerisation (ROMP) as a powerful technique for macromolecular engineering and synthesis of smart materials with well-defined structures. ROMP has attracted a considerable research attention recently particularly by industry largely due to the development of well-defined metal complexes as initiators and also because of the award of the Noble Prize for Chemistry in 2005 to three scientists (Chauvin, Grubbs, Schrock) for their contributions in this area. This chapter discusses several interesting examples in order to demonstrate that ROMP is a power tool in macromolecular engineering and that it allows the design and synthesis of polymers with novel topologies.

  4. Refinement of macromolecular structures against neutron data withSHELXL2013.

    Science.gov (United States)

    Gruene, Tim; Hahn, Hinrich W; Luebben, Anna V; Meilleur, Flora; Sheldrick, George M

    2014-02-01

    Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [ Acta Cryst. (1991), A 47 , 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

  5. Model Updating Nonlinear System Identification Toolbox Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ZONA Technology proposes to develop an enhanced model updating nonlinear system identification (MUNSID) methodology by adopting the flight data with state-of-the-art...

  6. Power system coherency and model reduction

    CERN Document Server

    Chow, Joe H

    2014-01-01

    This book provides a comprehensive treatment for understanding interarea modes in large power systems and obtaining reduced-order models using the coherency concept and selective modal analysis method.

  7. Regional Ocean Modeling System (ROMS): Samoa

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Regional Ocean Modeling System (ROMS) 7-day, 3-hourly forecast for the region surrounding the islands of Samoa at approximately 3-km resolution. While considerable...

  8. Systemic Therapy: A New Brief Intervention Model.

    Science.gov (United States)

    Searight, H. Russell; Openlander, Patrick

    1984-01-01

    Describes a newly developing mode of problem-oriented brief therapy. The systemic therapy model emphasizes the interactional context of clients' problems and represents an efficient intervention paradigm. (Author/JAC)

  9. Regional Ocean Modeling System (ROMS): CNMI

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Regional Ocean Modeling System (ROMS) 7-day, 3-hourly forecast for the region surrounding the Commonwealth of the Northern Mariana Islands (CNMI) at approximately...

  10. Regional Ocean Modeling System (ROMS): Guam

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Regional Ocean Modeling System (ROMS) 6-day, 3-hourly forecast for the region surrounding Guam at approximately 2-km resolution. While considerable effort has been...

  11. A Telecommunications Industry Primer: A Systems Model.

    Science.gov (United States)

    Obermier, Timothy R.; Tuttle, Ronald H.

    2003-01-01

    Describes the Telecommunications Systems Model to help technical educators and students understand the increasingly complex telecommunications infrastructure. Specifically looks at ownership and regulatory status, service providers, transport medium, network protocols, and end-user services. (JOW)

  12. Modeling Approaches and Systems Related to Structured Modeling.

    Science.gov (United States)

    1987-02-01

    Lasdon 򒾂> and Maturana 򒾃> for surveys of several modern systems. A -6- N NN- %0 CAMPS (Lucas and Mitra 򒾁>) -- Computer Assisted Mathe- %l...583-589. MATURANA , S. 򒾃>. "Comparative Analysis of Mathematical Modeling Systems," informal note, Graduate School of Manage- ment, UCLA, February

  13. Conceptual Modelling of Complex Production Systems

    Directory of Open Access Journals (Sweden)

    Nenad Perši

    2008-12-01

    Full Text Available Complex system dynamics, structure and behaviour performances call for a wide range of methods, algorithms and tools to reach a model capable of finding optimal performing parameters. In the modelling process, it is up to the analyst to select the appropriate combination of methods, algorithms and tools to express significant system performances. Such a methodology for designing complex systems should be based upon conceptual modelling to perform a sensitive analysis of different system levels and views, allowing system representations for developing computer models.Complex systems, such as business systems with a continuous-discrete production process, require a well organised supply chain highly reactive to production assortment changes. Aligning two different production components distinctive in their behaviour is especially delicate at the production parameters transition point. Such system performances require distinctive designing methods that can follow the double nature of the production process behaviour in accordance with their entities dynamics caused by assortment changes. Consequently, such systems need different conceptual presentations for their purpose to be realized from different views and aspects.

  14. Modeling of High Precision Positioning System

    Directory of Open Access Journals (Sweden)

    Giedrius Augustinavičius

    2014-02-01

    Full Text Available This paper presents the modeling of a flexure-based precisionpositioning system for micro-positioning uses. The positioningsystem is featured with monolithic architecture, flexure-basedjoints and ultra fine adjustment screws. Its workspace has beenevaluated via analytical approaches. Reduction mechanism isoptimally designed. The mathematical model of the positioningsystem has been derived, which is verified by resorting to finiteelement analysis (FEA. The established analytical and (FEAmodels are helpful for a reliable architecture optimization andperformance improvement of the positioning system.

  15. Ellipsoidal bag model for heavy quark system

    International Nuclear Information System (INIS)

    Bi Pinzhen; Fudan Univ., Shanghai

    1991-01-01

    The ellipsoidal bag model is used to describe heavy quark systems such as Qanti Q, Qanti Qg and Q 2 anti Q 2 . Instead of two step model, these states are described by an uniform picture. The potential derived from the ellipsoidal bag for Qanti Q is almost equivalent to the Cornell potential. For a Q 2 anti Q 2 system with large quark pair separation, an improvement of 70 MeV is obtained comparing with the spherical bag. (orig.)

  16. Hybrid Energy System Modeling in Modelica

    Energy Technology Data Exchange (ETDEWEB)

    William R. Binder; Christiaan J. J. Paredis; Humberto E. Garcia

    2014-03-01

    In this paper, a Hybrid Energy System (HES) configuration is modeled in Modelica. Hybrid Energy Systems (HES) have as their defining characteristic the use of one or more energy inputs, combined with the potential for multiple energy outputs. Compared to traditional energy systems, HES provide additional operational flexibility so that high variability in both energy production and consumption levels can be absorbed more effectively. This is particularly important when including renewable energy sources, whose output levels are inherently variable, determined by nature. The specific HES configuration modeled in this paper include two energy inputs: a nuclear plant, and a series of wind turbines. In addition, the system produces two energy outputs: electricity and synthetic fuel. The models are verified through simulations of the individual components, and the system as a whole. The simulations are performed for a range of component sizes, operating conditions, and control schemes.

  17. Model Reduction of Fuzzy Logic Systems

    Directory of Open Access Journals (Sweden)

    Zhandong Yu

    2014-01-01

    Full Text Available This paper deals with the problem of ℒ2-ℒ∞ model reduction for continuous-time nonlinear uncertain systems. The approach of the construction of a reduced-order model is presented for high-order nonlinear uncertain systems described by the T-S fuzzy systems, which not only approximates the original high-order system well with an ℒ2-ℒ∞ error performance level γ but also translates it into a linear lower-dimensional system. Then, the model approximation is converted into a convex optimization problem by using a linearization procedure. Finally, a numerical example is presented to show the effectiveness of the proposed method.

  18. System model development for nuclear thermal propulsion

    International Nuclear Information System (INIS)

    Walton, J.T.; Perkins, K.R.; Buksa, J.J.; Worley, B.A.; Dobranich, D.

    1992-01-01

    A critical enabling technology in the evolutionary development of nuclear thermal propulsion (NTP) is the ability to predict the system performance under a variety of operating conditions. Since October 1991, US (DOE), (DOD) and NASA have initiated critical technology development efforts for NTP systems to be used on Space Exploration Initiative (SEI) missions to the Moon and Mars. This paper presents the strategy and progress of an interagency NASA/DOE/DOD team for NTP system modeling. It is the intent of the interagency team to develop several levels of computer programs to simulate various NTP systems. An interagency team was formed for this task to use the best capabilities available and to assure appropriate peer review. The vision and strategy of the interagency team for developing NTP system models will be discussed in this paper. A review of the progress on the Level 1 interagency model is also presented

  19. Facilitating structure determination: workshop on robotics and automation in macromolecular crystallography

    International Nuclear Information System (INIS)

    Ralston, Corie; Cork, C.W.; McDermott, G.; Earnest, T.N.

    2006-01-01

    As part of the annual Advanced Light Source (ALS) and Stanford Synchrotron Radiation Laboratory (SSRL) Users' Meeting in October of this year, the macromolecular crystallography staff at both synchrotrons held a joint hands-on workshop to address automation issues in crystal mounting and data collection at the beamline. This paper describes the ALS portion of the workshop, while the accompanying paper reviews the SSRL workshop

  20. Measurement and Interpretation of Diffuse Scattering in X-Ray Diffraction for Macromolecular Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Michael E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-16

    X-ray diffraction from macromolecular crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering reflects the mean electron density in the unit cells of the crystal. The diffuse scattering arises from correlations in the variations of electron density that may occur from one unit cell to another, and therefore contains information about collective motions in proteins.

  1. Economic model of pipeline transportation systems

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W. F.

    1977-07-29

    The objective of the work reported here was to develop a model which could be used to assess the economic effects of energy-conservative technological innovations upon the pipeline industry. The model is a dynamic simulator which accepts inputs of two classes: the physical description (design parameters, fluid properties, and financial structures) of the system to be studied, and the postulated market (throughput and price) projection. The model consists of time-independent submodels: the fluidics model which simulates the physical behavior of the system, and the financial model which operates upon the output of the fluidics model to calculate the economics outputs. Any of a number of existing fluidics models can be used in addition to that developed as a part of this study. The financial model, known as the Systems, Science and Software (S/sup 3/) Financial Projection Model, contains user options whereby pipeline-peculiar characteristics can be removed and/or modified, so that the model can be applied to virtually any kind of business enterprise. The several dozen outputs are of two classes: the energetics and the economics. The energetics outputs of primary interest are the energy intensity, also called unit energy consumption, and the total energy consumed. The primary economics outputs are the long-run average cost, profit, cash flow, and return on investment.

  2. System Identification, Environmental Modelling, and Control System Design

    CERN Document Server

    Garnier, Hugues

    2012-01-01

    System Identification, Environmetric Modelling, and Control Systems Design is dedicated to Professor Peter Young on the occasion of his seventieth birthday. Professor Young has been a pioneer in systems and control, and over the past 45 years he has influenced many developments in this field. This volume is comprised of a collection of contributions by leading experts in system identification, time-series analysis, environmetric modelling and control system design – modern research in topics that reflect important areas of interest in Professor Young’s research career. Recent theoretical developments in and relevant applications of these areas are explored treating the various subjects broadly and in depth. The authoritative and up-to-date research presented here will be of interest to academic researcher in control and disciplines related to environmental research, particularly those to with water systems. The tutorial style in which many of the contributions are composed also makes the book suitable as ...

  3. Definitions of terms relating to individual macromolecules, macromolecular assemblies, polymer solutions, and amorphous bulk polymers (IUPAC Recommendations 2014)

    Czech Academy of Sciences Publication Activity Database

    Stepto, R.; Chang, T.; Kratochvíl, Pavel; Hess, M.; Horie, K.; Sato, T.; Vohlídal, J.

    2015-01-01

    Roč. 87, č. 1 (2015), s. 71-120 ISSN 0033-4545 Institutional support: RVO:61389013 Keywords : amorphous polymers * bulk polymers * IUPAC Polymer Division Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.615, year: 2015

  4. Ceruloplasmin: Macromolecular Assemblies with Iron-Containing Acute Phase Proteins

    Science.gov (United States)

    Samygina, Valeriya R.; Sokolov, Alexey V.; Bourenkov, Gleb; Petoukhov, Maxim V.; Pulina, Maria O.; Zakharova, Elena T.; Vasilyev, Vadim B.; Bartunik, Hans; Svergun, Dmitri I.

    2013-01-01

    Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein–protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1∶1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe3+ into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

  5. Mass distributions of a macromolecular assembly based on ...

    Indian Academy of Sciences (India)

    Unknown

    low resolution crystallographic structure of Lumbricus Er. (Royer et al 2000) established the stoichiometry to be. 144 globin chains arranged as 12 dodecamers tethered to. 36 linker chains, in agreement with the model proposed earlier (Vinogradov et al 1986) and the cryoEM 3D re- constructions (De Haas et al 1996a, b, c, ...

  6. Automated statistical modeling of analytical measurement systems

    International Nuclear Information System (INIS)

    Jacobson, J.J.

    1992-01-01

    The statistical modeling of analytical measurement systems at the Idaho Chemical Processing Plant (ICPP) has been completely automated through computer software. The statistical modeling of analytical measurement systems is one part of a complete quality control program used by the Remote Analytical Laboratory (RAL) at the ICPP. The quality control program is an integration of automated data input, measurement system calibration, database management, and statistical process control. The quality control program and statistical modeling program meet the guidelines set forth by the American Society for Testing Materials and American National Standards Institute. A statistical model is a set of mathematical equations describing any systematic bias inherent in a measurement system and the precision of a measurement system. A statistical model is developed from data generated from the analysis of control standards. Control standards are samples which are made up at precise known levels by an independent laboratory and submitted to the RAL. The RAL analysts who process control standards do not know the values of those control standards. The object behind statistical modeling is to describe real process samples in terms of their bias and precision and, to verify that a measurement system is operating satisfactorily. The processing of control standards gives us this ability

  7. Modelling the Replication Management in Information Systems

    Directory of Open Access Journals (Sweden)

    Cezar TOADER

    2017-01-01

    Full Text Available In the modern economy, the benefits of Web services are significant because they facilitates the activities automation in the framework of Internet distributed businesses as well as the cooperation between organizations through interconnection process running in the computer systems. This paper presents the development stages of a model for a reliable information system. This paper describes the communication between the processes within the distributed system, based on the message exchange, and also presents the problem of distributed agreement among processes. A list of objectives for the fault-tolerant systems is defined and a framework model for distributed systems is proposed. This framework makes distinction between management operations and execution operations. The proposed model promotes the use of a central process especially designed for the coordination and control of other application processes. The execution phases and the protocols for the management and the execution components are presented. This model of a reliable system could be a foundation for an entire class of distributed systems models based on the management of replication process.

  8. Generic Sensor Failure Modeling for Cooperative Systems

    Directory of Open Access Journals (Sweden)

    Georg Jäger

    2018-03-01

    Full Text Available The advent of cooperative systems entails a dynamic composition of their components. As this contrasts current, statically composed systems, new approaches for maintaining their safety are required. In that endeavor, we propose an integration step that evaluates the failure model of shared information in relation to an application’s fault tolerance and thereby promises maintainability of such system’s safety. However, it also poses new requirements on failure models, which are not fulfilled by state-of-the-art approaches. Consequently, this work presents a mathematically defined generic failure model as well as a processing chain for automatically extracting such failure models from empirical data. By examining data of an Sharp GP2D12 distance sensor, we show that the generic failure model not only fulfills the predefined requirements, but also models failure characteristics appropriately when compared to traditional techniques.

  9. Generic Sensor Failure Modeling for Cooperative Systems

    Science.gov (United States)

    Jäger, Georg; Zug, Sebastian

    2018-01-01

    The advent of cooperative systems entails a dynamic composition of their components. As this contrasts current, statically composed systems, new approaches for maintaining their safety are required. In that endeavor, we propose an integration step that evaluates the failure model of shared information in relation to an application’s fault tolerance and thereby promises maintainability of such system’s safety. However, it also poses new requirements on failure models, which are not fulfilled by state-of-the-art approaches. Consequently, this work presents a mathematically defined generic failure model as well as a processing chain for automatically extracting such failure models from empirical data. By examining data of an Sharp GP2D12 distance sensor, we show that the generic failure model not only fulfills the predefined requirements, but also models failure characteristics appropriately when compared to traditional techniques. PMID:29558435

  10. Macromolecular Coating Enables Tunable Selectivity in a Porous PDMS Matrix.

    Science.gov (United States)

    Winkeljann, Benjamin; Käsdorf, Benjamin T; Boekhoven, Job; Lieleg, Oliver

    2018-02-01

    Whether for laboratory use or clinical practice, many fields in Life Sciences require selective filtering. However, most existing filter systems lack the ability to easily tune their filtration behavior. Two key elements for efficient filtering are a high surface-to-volume ratio and the presence of suitable chemical groups which establish selectivity. In this study, an artificial PDMS-based capillary system with highly tunable selectivity properties is presented. The high surface-to-volume ratio of this filter system is generated by first embedding sugar fibers into a synthetic polymer matrix and then dissolving these fibers from the cured polymer. To functionalize this filter, the inner surface of the capillaries is coated with purified or synthetic macromolecules. Depending on the type of macromolecule used for filter functionalization, selective sieving is observed based on steric hindrance, electrostatic binding, electrostatic repulsion, or specific binding interactions. Furthermore, it is demonstrated that enzymes can be immobilized in the capillary system which allows for performing multiple cycles of enzymatic reactions with the same batch of enzymes and without the need to separate the enzymes from their reaction products. In addition to lab-scale filtration and enzyme immobilization applications demonstrated here, the functionalized porous PDMS matrix may also be used to test binding interactions between different molecules. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. A Sensitized Emission Based Calibration of FRET Efficiency for Probing the Architecture of Macromolecular Machines.

    Science.gov (United States)

    Joglekar, Ajit; Chen, Renjie; Lawrimore, Joshua

    2013-01-01

    Macromolecular machines participate in almost every cell biological function. These machines can take the form of well-defined protein structures such as the kinetochore, or more loosely organized protein assemblies like the endocytic coat. The protein architecture of these machines-the arrangement of multiple copies of protein subunits at the nanoscale, is necessary for understanding their cell biological function and biophysical mechanism. Defining this architecture in vivo presents a major challenge. High density of protein molecules within macromolecular machines severely limits the effectiveness of super-resolution microscopy. However, this density is ideal for Forster Resonance Energy Transfer (FRET), which can determine the proximity between neighboring molecules. Here, we present a simple FRET quantitation scheme that calibrates a standard epifluorescence microscope for measuring donor-acceptor separations. This calibration can be used to deduce FRET efficiency fluorescence intensity measurements. This method will allow accurate determination of FRET efficiency over a wide range of values and FRET pair number. It will also allow dynamic FRET measurements with high spatiotemporal resolution under cell biological conditions. Although the poor maturation efficiency of genetically encoded fluorescent proteins presents a challenge, we show that its effects can be alleviated. To demonstrate this methodology, we probe the in vivo architecture of the γ-Tubulin Ring. Our technique can be applied to study the architecture and dynamics of a wide range of macromolecular machines.

  12. Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.

    Science.gov (United States)

    Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

    2013-11-01

    The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation. © 2013 FEBS.

  13. Fundamental and biotechnological applications of neutron scattering measurements for macromolecular dynamics.

    Science.gov (United States)

    Tehei, Moeava; Daniel, Roy; Zaccai, Giuseppe

    2006-09-01

    To explore macromolecular dynamics on the picosecond timescale, we used neutron spectroscopy. First, molecular dynamics were analyzed for the hyperthermophile malate dehydrogenase from Methanococcus jannaschii and a mesophilic homologue, the lactate dehydrogenase from Oryctolagus cunniculus muscle. Hyperthermophiles have elaborate molecular mechanisms of adaptation to extremely high temperature. Using a novel elastic neutron scattering approach that provides independent measurements of the global flexibility and of the structural resilience (rigidity), we have demonstrated that macromolecular dynamics represents one of these molecular mechanisms of thermoadaptation. The flexibilities were found to be similar for both enzymes at their optimal activity temperature and the resilience is higher for the hyperthermophilic protein. Secondly, macromolecular motions were examined in a native and immobilized dihydrofolate reductase (DHFR) from Escherichia coli. The immobilized mesophilic enzyme has increased stability and decreased activity, so that its properties are changed to resemble those of the thermophilic enzyme. Are these changes reflected in dynamical behavior? For this study, we performed quasielastic neutron scattering measurements to probe the protein motions. The residence time is 7.95 ps for the native DHFR and 20.36 ps for the immobilized DHFR. The average height of the potential barrier to local motions is therefore increased in the immobilized DHFR, with a difference in activation energy equal to 0.54 kcal/mol, which is, using the theoretical rate equation, of the same order than expected from calculation.

  14. Energy model in regional energy system

    International Nuclear Information System (INIS)

    Mura, P.G.; Baccoli, R.; Carlini, U.; Innamorati, R.; Mariotti, S.

    2005-01-01

    In this report is presented a computational model for analysis of energy, materials and mass flux in a complex energy system, at regional scale level. Specifically is described a calculation model of electric power generation for emission forecasting of CO 2 , SO x , NO x , particulate matter, ashes, limestone, chalks [it

  15. Immune System Model Calibration by Genetic Algorithm

    NARCIS (Netherlands)

    Presbitero, A.; Krzhizhanovskaya, V.; Mancini, E.; Brands, R.; Sloot, P.

    2016-01-01

    We aim to develop a mathematical model of the human immune system for advanced individualized healthcare where medication plan is fine-tuned to fit a patient's conditions through monitored biochemical processes. One of the challenges is calibrating model parameters to satisfy existing experimental

  16. Analytical system dynamics modeling and simulation

    CERN Document Server

    Fabien, Brian C

    2008-01-01

    This book offering a modeling technique based on Lagrange's energy method includes 125 worked examples. Using this technique enables one to model and simulate systems as diverse as a six-link, closed-loop mechanism or a transistor power amplifier.

  17. System level modelling with open source tools

    DEFF Research Database (Denmark)

    Jakobsen, Mikkel Koefoed; Madsen, Jan; Niaki, Seyed Hosein Attarzadeh

    , called ForSyDe. ForSyDe is available under the open Source approach, which allows small and medium enterprises (SME) to get easy access to advanced modeling capabilities and tools. We give an introduction to the design methodology through the system level modeling of a simple industrial use case, and we...

  18. Modelling and control of dynamic systems using gaussian process models

    CERN Document Server

    Kocijan, Juš

    2016-01-01

    This monograph opens up new horizons for engineers and researchers in academia and in industry dealing with or interested in new developments in the field of system identification and control. It emphasizes guidelines for working solutions and practical advice for their implementation rather than the theoretical background of Gaussian process (GP) models. The book demonstrates the potential of this recent development in probabilistic machine-learning methods and gives the reader an intuitive understanding of the topic. The current state of the art is treated along with possible future directions for research. Systems control design relies on mathematical models and these may be developed from measurement data. This process of system identification, when based on GP models, can play an integral part of control design in data-based control and its description as such is an essential aspect of the text. The background of GP regression is introduced first with system identification and incorporation of prior know...

  19. Human performance modeling for system of systems analytics :soldier fatigue.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Campbell, James E.; Miller, Dwight Peter

    2005-10-01

    The military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives as can be seen in the Department of Defense's (DoD) Defense Modeling and Simulation Office's (DMSO) Master Plan (DoD 5000.59-P 1995). To this goal, the military is currently spending millions of dollars on programs devoted to HPM in various military contexts. Examples include the Human Performance Modeling Integration (HPMI) program within the Air Force Research Laboratory, which focuses on integrating HPMs with constructive models of systems (e.g. cockpit simulations) and the Navy's Human Performance Center (HPC) established in September 2003. Nearly all of these initiatives focus on the interface between humans and a single system. This is insufficient in the era of highly complex network centric SoS. This report presents research and development in the area of HPM in a system-of-systems (SoS). Specifically, this report addresses modeling soldier fatigue and the potential impacts soldier fatigue can have on SoS performance.

  20. Tuning the properties of an anthracene-based PPE-PPV copolymer by fine variation of its macromolecular parameters

    Czech Academy of Sciences Publication Activity Database

    Tinti, F.; Sabir, F. K.; Gazzano, M.; Righi, S.; Ulbricht, C.; Usluer, Ö.; Pokorná, Veronika; Cimrová, Věra; Yohannes, T.; Egbe, D. A. M.; Camaioni, N.

    2013-01-01

    Roč. 3, č. 19 (2013), s. 6972-6980 ISSN 2046-2069 R&D Projects: GA ČR GAP106/12/0827; GA ČR(CZ) GA13-26542S Institutional support: RVO:61389013 Keywords : anthracene-containing PPE-PPV copolymer * macromolecular parameters * structural and transport properties Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.708, year: 2013

  1. Predictive Model of Systemic Toxicity (SOT)

    Science.gov (United States)

    In an effort to ensure chemical safety in light of regulatory advances away from reliance on animal testing, USEPA and L’Oréal have collaborated to develop a quantitative systemic toxicity prediction model. Prediction of human systemic toxicity has proved difficult and remains a ...

  2. CTBT Integrated Verification System Evaluation Model

    Energy Technology Data Exchange (ETDEWEB)

    Edenburn, M.W.; Bunting, M.L.; Payne, A.C. Jr.

    1997-10-01

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia`s Monitoring Systems and Technology Center and has been funded by the US Department of Energy`s Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, top-level, modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM`s unique features is that it integrates results from the various CTBT sensor technologies (seismic, infrasound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection) and location accuracy of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system`s performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. This report describes version 1.2 of IVSEM.

  3. Modeling a Longitudinal Relational Research Data Systems

    Science.gov (United States)

    Olsen, Michelle D. Hunt

    2010-01-01

    A study was conducted to propose a research-based model for a longitudinal data research system that addressed recommendations from a synthesis of literature related to: (1) needs reported by the U.S. Department of Education, (2) the twelve mandatory elements that define federally approved state longitudinal data systems (SLDS), (3) the…

  4. Economic Models and Algorithms for Distributed Systems

    CERN Document Server

    Neumann, Dirk; Altmann, Jorn; Rana, Omer F

    2009-01-01

    Distributed computing models for sharing resources such as Grids, Peer-to-Peer systems, or voluntary computing are becoming increasingly popular. This book intends to discover fresh avenues of research and amendments to existing technologies, aiming at the successful deployment of commercial distributed systems

  5. Installed water resource modelling systems for catchment ...

    African Journals Online (AJOL)

    Following international trends there are a growing number of modelling systems being installed for integrated water resource management, in Southern Africa. Such systems are likely to be installed for operational use in ongoing learning, research, strategic planning and consensus-building amongst stakeholders in the ...

  6. Knowledge Management System Model for Learning Organisations

    Science.gov (United States)

    Amin, Yousif; Monamad, Roshayu

    2017-01-01

    Based on the literature of knowledge management (KM), this paper reports on the progress of developing a new knowledge management system (KMS) model with components architecture that are distributed over the widely-recognised socio-technical system (STS) aspects to guide developers for selecting the most applicable components to support their KM…

  7. Eclectic Model in the Malaysian Education System

    Science.gov (United States)

    Othman, Nooraini; Mohamad, Khairul Azmi; Ilmuwan, Yayasan

    2011-01-01

    The present work aims at analysing the adoption of eclectic model in the Malaysian education system. The analysis is specifically looked from the angle of Islam and the Muslims. Malaysia has a long history of education system developments, from pre to post independence of the country. From what was initially traditional, modernity later came to…

  8. Modelling of functional systems of managerial accounting

    Directory of Open Access Journals (Sweden)

    O.V. Fomina

    2017-12-01

    Full Text Available The modern stage of managerial accounting development takes place under the powerful influence of managerial innovations. The article aimed at the development of integrational model of budgeting and the system of balanced indices in the system of managerial accounting that will contribute the increasing of relevance for making managerial decisions by managers of different levels management. As a result of the study the author proposed the highly pragmatical integration model of budgeting and system of the balanced indices in the system of managerial accounting, which is realized by the development of the system of gathering, consolidation, analysis, and interpretation of financial and nonfinancial information, contributes the increasing of relevance for making managerial decisions on the base of coordination and effective and purpose orientation both strategical and operative resources of an enterprise. The effective integrational process of the system components makes it possible to distribute limited resources rationally taking into account prospective purposes and strategic initiatives, to carry

  9. Degradation Modelling for Health Monitoring Systems

    International Nuclear Information System (INIS)

    Stetter, R; Witczak, M

    2014-01-01

    Condition-monitoring plays an increasingly important role for technical processes in order to improve reliability, availability, maintenance and lifetime of equipment. With increasing demands for efficiency and product quality, plus progress in the integration of automatic control systems in high-cost mechatronic and critical safety processes, the field of health monitoring is gaining interest. A similar research field is concerned with an estimation of the remaining useful life. A central question in these fields is the modelling of degradation; degradation is a process of a gradual and irreversible accumulation of damage which will finally result in a failure of the system. This paper is based on a current research project and explores various degradation modelling techniques. These results are explained on the basis of an industrial product – a system for the generation of health status information for pump systems. The result of this fuzzy-logic based system is a single number indicating the current health of a pump system

  10. World energy projection system: Model documentation

    International Nuclear Information System (INIS)

    1992-06-01

    The World Energy Project System (WEPS) is an accounting framework that incorporates projects from independently documented models and assumptions about the future energy intensity of economic activity (ratios of total energy consumption divided by gross domestic product) and about the rate of incremental energy requirements met by hydropower, geothermal, coal, and natural gas to produce projections of world energy consumption published annually by the Energy Information Administration (EIA) in the International Energy Outlook (IEO) (Figure 1). Two independently documented models presented in Figure 1, the Oil Market Simulation (OMS) model and the World Integrated Nuclear Evaluation System (WINES) provide projections of oil and nuclear power consumption published in the IEO. Output from a third independently documented model, and the International Coal Trade Model (ICTM), is not published in the IEO but is used in WEPS as a supply check on projections of world coal consumption produced by WEPS and published in the IEO. A WEPS model of natural gas production documented in this report provides the same type of implicit supply check on the WEPS projections of world natural gas consumption published in the IEO. Two additional models are included in Figure 1, the OPEC Capacity model and the Non-OPEC Oil Production model. These WEPS models provide inputs to the OMS model and are documented in this report

  11. OFFl Models: Novel Schema for Dynamical Modeling of Biological Systems.

    Directory of Open Access Journals (Sweden)

    C Brandon Ogbunugafor

    Full Text Available Flow diagrams are a common tool used to help build and interpret models of dynamical systems, often in biological contexts such as consumer-resource models and similar compartmental models. Typically, their usage is intuitive and informal. Here, we present a formalized version of flow diagrams as a kind of weighted directed graph which follow a strict grammar, which translate into a system of ordinary differential equations (ODEs by a single unambiguous rule, and which have an equivalent representation as a relational database. (We abbreviate this schema of "ODEs and formalized flow diagrams" as OFFL. Drawing a diagram within this strict grammar encourages a mental discipline on the part of the modeler in which all dynamical processes of a system are thought of as interactions between dynamical species that draw parcels from one or more source species and deposit them into target species according to a set of transformation rules. From these rules, the net rate of change for each species can be derived. The modeling schema can therefore be understood as both an epistemic and practical heuristic for modeling, serving both as an organizational framework for the model building process and as a mechanism for deriving ODEs. All steps of the schema beyond the initial scientific (intuitive, creative abstraction of natural observations into model variables are algorithmic and easily carried out by a computer, thus enabling the future development of a dedicated software implementation. Such tools would empower the modeler to consider significantly more complex models than practical limitations might have otherwise proscribed, since the modeling framework itself manages that complexity on the modeler's behalf. In this report, we describe the chief motivations for OFFL, carefully outline its implementation, and utilize a range of classic examples from ecology and epidemiology to showcase its features.

  12. Compiling models into real-time systems

    International Nuclear Information System (INIS)

    Dormoy, J.L.; Cherriaux, F.; Ancelin, J.

    1992-08-01

    This paper presents an architecture for building real-time systems from models, and model-compiling techniques. This has been applied for building a real-time model-based monitoring system for nuclear plants, called KSE, which is currently being used in two plants in France. We describe how we used various artificial intelligence techniques for building it: a model-based approach, a logical model of its operation, a declarative implementation of these models, and original knowledge-compiling techniques for automatically generating the real-time expert system from those models. Some of those techniques have just been borrowed from the literature, but we had to modify or invent other techniques which simply did not exist. We also discuss two important problems, which are often underestimated in the artificial intelligence literature: size, and errors. Our architecture, which could be used in other applications, combines the advantages of the model-based approach with the efficiency requirements of real-time applications, while in general model-based approaches present serious drawbacks on this point

  13. Compiling models into real-time systems

    International Nuclear Information System (INIS)

    Dormoy, J.L.; Cherriaux, F.; Ancelin, J.

    1992-08-01

    This paper presents an architecture for building real-time systems from models, and model-compiling techniques. This has been applied for building a real-time model-base monitoring system for nuclear plants, called KSE, which is currently being used in two plants in France. We describe how we used various artificial intelligence techniques for building it: a model-based approach, a logical model of its operation, a declarative implementation of these models, and original knowledge-compiling techniques for automatically generating the real-time expert system from those models. Some of those techniques have just been borrowed from the literature, but we had to modify or invent other techniques which simply did not exist. We also discuss two important problems, which are often underestimated in the artificial intelligence literature: size, and errors. Our architecture, which could be used in other applications, combines the advantages of the model-based approach with the efficiency requirements of real-time applications, while in general model-based approaches present serious drawbacks on this point

  14. Models for large superconducting toroidal magnet systems

    International Nuclear Information System (INIS)

    Arendt, F.; Brechna, H.; Erb, J.; Komarek, P.; Krauth, H.; Maurer, W.

    1976-01-01

    Prior to the design of large GJ toroidal magnet systems it is appropriate to procure small scale models, which can simulate their pertinent properties and allow to investigate their relevant phenomena. The important feature of the model is to show under which circumstances the system performance can be extrapolated to large magnets. Based on parameters such as the maximum magnetic field and the current density, the maximum tolerable magneto-mechanical stresses, a simple method of designing model magnets is presented. It is shown how pertinent design parameters are changed when the toroidal dimensions are altered. In addition some conductor cost estimations are given based on reactor power output and wall loading

  15. Modeling and simulation of discrete event systems

    CERN Document Server

    Choi, Byoung Kyu

    2013-01-01

    Computer modeling and simulation (M&S) allows engineers to study and analyze complex systems. Discrete-event system (DES)-M&S is used in modern management, industrial engineering, computer science, and the military. As computer speeds and memory capacity increase, so DES-M&S tools become more powerful and more widely used in solving real-life problems. Based on over 20 years of evolution within a classroom environment, as well as on decades-long experience in developing simulation-based solutions for high-tech industries, Modeling and Simulation of Discrete-Event Systems is the only book on

  16. Modeling the heart and the circulatory system

    CERN Document Server

    2015-01-01

    The book comprises contributions by some of the most respected scientists in the field of mathematical modeling and numerical simulation of the human cardiocirculatory system. The contributions cover a wide range of topics, from the preprocessing of clinical data to the development of mathematical equations, their numerical solution, and both in-vivo and in-vitro validation. They discuss the flow in the systemic arterial tree and the complex electro-fluid-mechanical coupling in the human heart. Many examples of patient-specific simulations are presented. This book is addressed to all scientists interested in the mathematical modeling and numerical simulation of the human cardiocirculatory system.

  17. Quantitative Models and Analysis for Reactive Systems

    DEFF Research Database (Denmark)

    Thrane, Claus

    The majority of modern software and hardware systems are reactive systems, where input provided by the user (possibly another system) and the output of the system is exchanged continuously throughout the (possibly) indefinite execution of the system. Natural examples include control systems, mobi......, energy consumption, latency, mean-time to failure, and cost. For systems integrated in mass-market products, the ability to quantify trade-offs between performance and robustness, under given technical and economic constraints, is of strategic importance....... by the environment in which they are embedded. This thesis studies the semantics and properties of a model-based framework for re- active systems, in which models and specifications are assumed to contain quantifiable information, such as references to time or energy. Our goal is to develop a theory of approximation......, in terms of a new mathematical basis for systems modeling which can incompas behavioural properties as well as environmental constraints. They continue by pointing out that, continuous performance and robustness measures are paramount when dealing with physical resource levels such as clock frequency...

  18. An Integrated Ecological Modeling System for Assessing ...

    Science.gov (United States)

    We demonstrate a novel, spatially explicit assessment of the current condition of aquatic ecosystem services, with limited sensitivity analysis for the atmospheric contaminant mercury. The Integrated Ecological Modeling System (IEMS) forecasts water quality and quantity, habitat suitability for aquatic biota, fish biomasses, population densities, productivities, and contamination by methylmercury across headwater watersheds. We applied this IEMS to the Coal River Basin (CRB), West Virginia (USA), an 8-digit hydrologic unit watershed, by simulating a network of 97 stream segments using the SWAT watershed model, a watershed mercury loading model, the WASP water quality model, the PiSCES fish community estimation model, a fish habitat suitability model, the BASS fish community and bioaccumulation model, and an ecoservices post-processer. Model application was facilitated by automated data retrieval and model setup and updated model wrappers and interfaces for data transfers between these models from a prior study. This companion study evaluates baseline predictions of ecoservices provided for 1990 – 2010 for the population of streams in the CRB and serves as a foundation for future model development. Published in the journal, Ecological Modeling. Highlights: • Demonstrate a spatially-explicit IEMS for multiple scales. • Design a flexible IEMS for

  19. Modelling dependable systems using hybrid Bayesian networks

    International Nuclear Information System (INIS)

    Neil, Martin; Tailor, Manesh; Marquez, David; Fenton, Norman; Hearty, Peter

    2008-01-01

    A hybrid Bayesian network (BN) is one that incorporates both discrete and continuous nodes. In our extensive applications of BNs for system dependability assessment, the models are invariably hybrid and the need for efficient and accurate computation is paramount. We apply a new iterative algorithm that efficiently combines dynamic discretisation with robust propagation algorithms on junction tree structures to perform inference in hybrid BNs. We illustrate its use in the field of dependability with two example of reliability estimation. Firstly we estimate the reliability of a simple single system and next we implement a hierarchical Bayesian model. In the hierarchical model we compute the reliability of two unknown subsystems from data collected on historically similar subsystems and then input the result into a reliability block model to compute system level reliability. We conclude that dynamic discretisation can be used as an alternative to analytical or Monte Carlo methods with high precision and can be applied to a wide range of dependability problems

  20. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Laurence, Ted Alfred [Univ. of California, Berkeley, CA (United States)

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  1. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    International Nuclear Information System (INIS)

    Laurence, Ted Alfred

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  2. Stochastic Modelling Of The Repairable System

    Directory of Open Access Journals (Sweden)

    Andrzejczak Karol

    2015-11-01

    Full Text Available All reliability models consisting of random time factors form stochastic processes. In this paper we recall the definitions of the most common point processes which are used for modelling of repairable systems. Particularly this paper presents stochastic processes as examples of reliability systems for the support of the maintenance related decisions. We consider the simplest one-unit system with a negligible repair or replacement time, i.e., the unit is operating and is repaired or replaced at failure, where the time required for repair and replacement is negligible. When the repair or replacement is completed, the unit becomes as good as new and resumes operation. The stochastic modelling of recoverable systems constitutes an excellent method of supporting maintenance related decision-making processes and enables their more rational use.

  3. A system model for water management.

    Science.gov (United States)

    Schenk, Colin; Roquier, Bastien; Soutter, Marc; Mermoud, André

    2009-03-01

    Although generally accepted as a necessary step to improve water management and planning, integrated water resources management (IWRM) methodology does not provide a clear definition of what should be integrated. The various water-related issues that IWRM might encompass are well documented in the literature, but they are generally addressed separately. Therefore, water management lacks a holistic, systems-based description, with a special emphasis on the interrelations between issues. This article presents such a system model for water management, including a graphical representation and textual descriptions of the various water issues, their components, and their interactions. This model is seen as an aide-memoire and a generic reference, providing background knowledge helping to elicit actual system definitions, in possible combination with other participatory systems approaches. The applicability of the model is demonstrated through its application to two test case studies.

  4. Intelligent Mechatronic Systems Modeling, Control and Diagnosis

    CERN Document Server

    Merzouki, Rochdi; Pathak, Pushparaj Mani; Ould Bouamama, Belkacem

    2013-01-01

    Acting as a support resource for practitioners and professionals looking to advance their understanding of complex mechatronic systems, Intelligent Mechatronic Systems explains their design and recent developments from first principles to practical applications. Detailed descriptions of the mathematical models of complex mechatronic systems, developed from fundamental physical relationships, are built on to develop innovative solutions with particular emphasis on physical model-based control strategies. Following a concurrent engineering approach, supported by industrial case studies, and drawing on the practical experience of the authors, Intelligent Mechatronic Systems covers range of topic and includes:  • An explanation of a common graphical tool for integrated design and its uses from modeling and simulation to the control synthesis • Introductions to key concepts such as different means of achieving fault tolerance, robust overwhelming control and force and impedance control • Dedicated chapters ...

  5. Mineral Grains, Dimples, and Hot Volcanic Organic Streams: Dynamic Geological Backstage of Macromolecular Evolution.

    Science.gov (United States)

    Skoblikow, Nikolai E; Zimin, Andrei A

    2018-03-28

    The hypothesis of hot volcanic organic stream as the most probable and geologically plausible environment for abiogenic polycondensation is proposed. The primary synthesis of organic compounds is considered as result of an explosive volcanic (perhaps, meteorite-induced) eruption. The eruption was accompanied by a shock wave propagating in the primeval atmosphere and resulting in the formation of hot cloud of simple organic compounds-aldehydes, alcohols, amines, amino alcohols, nitriles, and amino acids-products, which are usually obtained under the artificial conditions in the spark-discharge experiments. The subsequent cooling of the organic cloud resulted in a gradual condensation and a serial precipitation of organic compounds (in order of decreasing boiling point values) into the liquid phase forming a hot, viscous and muddy organic stream (named "lithorheos"). That stream-even if the time of its existence was short-is considered here as a geologically plausible environment for abiogenic polycondensation. The substances successively prevailing in such a stream were cyanamide, acetamide, formamide, glycolonitrile, acetonitrile. An important role was played by mineral (especially, phosphate-containing) grains (named "lithosomes"), whose surface was modified with heterocyclic nitrogen compounds synthesized in the course of eruption. When such grains got into hot organic streams, their surface catalytic centers (named "lithozymes") played a decisive role in the emergence, facilitation and maintenance of prebiotic reactions and key processes characteristic of living systems. Owing to its cascade structure, the stream was a factor underlying the formation of mineral-polymeric aggregates (named "lithocytes") in the small natural streambed cavities (dimples)-as well as a factor of their further spread within larger geological locations which played a role of chemo-ecological niches. All three main stages of prebiotic evolution (primary organic synthesis

  6. Brand Equity Evolution: a System Dynamics Model

    Directory of Open Access Journals (Sweden)

    Edson Crescitelli

    2009-04-01

    Full Text Available One of the greatest challenges in brand management lies in monitoring brand equity over time. This paper aimsto present a simulation model able to represent this evolution. The model was drawn on brand equity concepts developed by Aaker and Joachimsthaler (2000, using the system dynamics methodology. The use ofcomputational dynamic models aims to create new sources of information able to sensitize academics and managers alike to the dynamic implications of their brand management. As a result, an easily implementable model was generated, capable of executing continuous scenario simulations by surveying casual relations among the variables that explain brand equity. Moreover, the existence of a number of system modeling tools will allow extensive application of the concepts used in this study in practical situations, both in professional and educational settings

  7. Identification models of the nervous system.

    Science.gov (United States)

    Zipser, D

    1992-01-01

    It has been widely observed that when artificial neural networks are trained by supervised learning to do computations that also occur in the nervous system, the behavior of the model neurons often closely resembles that of the real neurons involved in the task. It is not immediately clear why this should be the case or what use can be made of models generated by supervised learning. Here, recent developments are reviewed and analysed in an attempt to clarify these issues. This analysis is facilitated by treating supervised learning models of the brain as a special case of system identification, a general and well-studied modeling paradigm. The neural systems identification paradigm provides a systematic way to generate realistic models starting with a high-level description of a hypothesized computation and some architectural and physiological constraints about the area being modeled. There is no inherent limitation to the realism that can be incorporated into identification models. This approach eliminates the need to find neural implementation algorithms by ad hoc means and provides neuroscientists with a convenient way to build models that account for observed data.

  8. Prototype models for the MOIRA computerised system

    Energy Technology Data Exchange (ETDEWEB)

    Monte, Luigi [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente; Hakanson, Lars [Uppsala, Univ. (Sweden). Institute of Earth Sciences; Brittain, John [Oslo, Univ. (Norway). Zoological Museum

    1997-06-01

    The main aim of the present report is to describe selected models and the principles of the Decision Analysis theory that will be applied to develop the model-based computerised system `MOIRA`. A dose model and a model for predicting radiocaesium migration in lakes and the effects of countermeasures to reduce the contamination levels in the components of lacustrine system are described in detail. The principles for developing prototype models for predicting the migration of {sup 90}Sr in lake abiotic and biotic components are discussed. The environmental models described in the report are based on the use of `collective parameters` which due to mutual compensation effects of different phenomena occurring in complex systems, show low variability when the environmental conditions change. Use of such `collective parameters` not only increases the predictive power of the models, but also increases the practical applicability of the model. Among the main results described in the report, the development of an objective hierarchy table for evaluating the effectiveness of a countermeasure when the economic, social and ecological impacts are accounted for, deserves special attention.

  9. An Alternative Hypothesis for How Microgravity Improves Macromolecular Crystal Quality

    Science.gov (United States)

    Pusey, Marc

    2003-01-01

    There is a substantial body of experimental evidence, from this and other laboratories, that strongly suggests that for many proteins crystal nucleation and growth is by addition of associated species that are preformed by reversible concentration-driven self association processes in the bulk solution. We have developed a self-association model for the crystal nucleation and growth of the protein chicken egg lysozyme. The model accounts for the obtained crystal symmetry, explains the observed surface structures, and shows the importance of the symmetry obtained by self-association in solution to the process as a whole. This model also offers a possible mechanism for fluid flow effects on the growth process and how microgravity may affect it. While a single lysozyme molecule is relatively small an octamer in the 43 helix configuration (the proposed average sized growth unit) would have a M.W. approx. 115,000 and dimensions of 5.6 x 5.6 x 7.6 nm. Direct AFM measurements of growth unit incorporation indicate that units as wide as 11.2 nm and as long as 11.4 nm (a 24-mer) commonly attach to the crystal. AFM results from Weichmann et al. (Ultramicroscopy 86, 159-166, 2001) suggest that associated species of up to 40-mers in size add to the (101) faces. These measurements reflect the sizes of units that both added and desorbed from the crystal surface. The larger and less isotropic the associated species the more likely that it will be oriented to some degree in a flowing boundary layer, even at the low flow velocities measured about macromolecule crystals. On Earth, concentration gradient driven flow will maintain a high interfacial concentration, i.e., a high level (essentially that of the bulk solution) of solute association at the interface and higher growth rate. Higher growth rates mean an increased probability that misaligned growth units are trapped by subsequent growth layers before they can be desorbed and try again, or that the desorbing species is more likely

  10. Intrinsic Uncertainties in Modeling Complex Systems.

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Curtis S; Bramson, Aaron L.; Ames, Arlo L.

    2014-09-01

    Models are built to understand and predict the behaviors of both natural and artificial systems. Because it is always necessary to abstract away aspects of any non-trivial system being modeled, we know models can potentially leave out important, even critical elements. This reality of the modeling enterprise forces us to consider the prospective impacts of those effects completely left out of a model - either intentionally or unconsidered. Insensitivity to new structure is an indication of diminishing returns. In this work, we represent a hypothetical unknown effect on a validated model as a finite perturba- tion whose amplitude is constrained within a control region. We find robustly that without further constraints, no meaningful bounds can be placed on the amplitude of a perturbation outside of the control region. Thus, forecasting into unsampled regions is a very risky proposition. We also present inherent difficulties with proper time discretization of models and representing in- herently discrete quantities. We point out potentially worrisome uncertainties, arising from math- ematical formulation alone, which modelers can inadvertently introduce into models of complex systems. Acknowledgements This work has been funded under early-career LDRD project #170979, entitled "Quantify- ing Confidence in Complex Systems Models Having Structural Uncertainties", which ran from 04/2013 to 09/2014. We wish to express our gratitude to the many researchers at Sandia who con- tributed ideas to this work, as well as feedback on the manuscript. In particular, we would like to mention George Barr, Alexander Outkin, Walt Beyeler, Eric Vugrin, and Laura Swiler for provid- ing invaluable advice and guidance through the course of the project. We would also like to thank Steven Kleban, Amanda Gonzales, Trevor Manzanares, and Sarah Burwell for their assistance in managing project tasks and resources.

  11. Reliability modeling of an engineered barrier system

    International Nuclear Information System (INIS)

    Ananda, M.M.A.; Singh, A.K.; Flueck, J.A.

    1993-01-01

    The Weibull distribution is widely used in reliability literature as a distribution of time to failure, as it allows for both increasing failure rate (IFR) and decreasing failure rate (DFR) models. It has also been used to develop models for an engineered barrier system (EBS), which is known to be one of the key components in a deep geological repository for high level radioactive waste (HLW). The EBS failure time can more realistically be modelled by an IFR distribution, since the failure rate for the EBS is not expected to decrease with time. In this paper, we use an IFR distribution to develop a reliability model for the EBS

  12. Modelling and Analyses of Embedded Systems Design

    DEFF Research Database (Denmark)

    Brekling, Aske Wiid

    We present the MoVES languages: a language with which embedded systems can be specified at a stage in the development process where an application is identified and should be mapped to an execution platform (potentially multi- core). We give a formal model for MoVES that captures and gives......-based verification is a promising approach for assisting developers of embedded systems. We provide examples of system verifications that, in size and complexity, point in the direction of industrially-interesting systems....... semantics to the elements of specifications in the MoVES language. We show that even for seem- ingly simple systems, the complexity of verifying real-time constraints can be overwhelming - but we give an upper limit to the size of the search-space that needs examining. Furthermore, the formal model exposes...

  13. Multilevel Flow Modeling of Domestic Heating Systems

    DEFF Research Database (Denmark)

    Hu, Junjie; Lind, Morten; You, Shi

    2012-01-01

    of complementing this reasoning methodology. Domestic heating systems, as the main resource to meet the thermal requirements of end-users, have different implementations in Europe in order to achieve various degrees of controllability and heating efficiencies. As all the heating systems serve the same basic needs...... i.e. supplying and transferring thermal energy, it is off interest to use MFM to investigate similarities and differences between different implementations. In this paper, three typical domestic European heating systems, which differ from each other in the number of temperature sensors and auxiliary...... components e.g. storage tanks, are modeled using the MFM methodology. Both the goals and functions of material and energy processes and the control functions of the heating systems are represented in the MFM models. It is found that varying the physical system setup results in only little differences among...

  14. Modelling supervisory controller for hybrid power systems

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, A.; Bindner, H.; Lundsager, P. [Risoe National Lab., Roskilde (Denmark); Jannerup, O. [Technical Univ. of Denmark, Dept. of Automation, Lyngby (Denmark)

    1999-03-01

    Supervisory controllers are important to achieve optimal operation of hybrid power systems. The performance and economics of such systems depend mainly on the control strategy for switching on/off components. The modular concept described in this paper is an attempt to design standard supervisory controllers that could be used in different applications, such as village power and telecommunication applications. This paper presents some basic aspects of modelling and design of modular supervisory controllers using the object-oriented modelling technique. The functional abstraction hierarchy technique is used to formulate the control requirements and identify the functions of the control system. The modular algorithm is generic and flexible enough to be used with any system configuration and several goals (different applications). The modularity includes accepting modification of system configuration and goals during operation with minor or no changes in the supervisory controller. (au)

  15. Mathematical Modeling of Hybrid Electrical Engineering Systems

    Directory of Open Access Journals (Sweden)

    A. A. Lobaty

    2016-01-01

    Full Text Available A large class of systems that have found application in various industries and households, electrified transportation facilities and energy sector has been classified as electrical engineering systems. Their characteristic feature is a combination of continuous and discontinuous modes of operation, which is reflected in the appearance of a relatively new term “hybrid systems”. A wide class of hybrid systems is pulsed DC converters operating in a pulse width modulation, which are non-linear systems with variable structure. Using various methods for linearization it is possible to obtain linear mathematical models that rather accurately simulate behavior of such systems. However, the presence in the mathematical models of exponential nonlinearities creates considerable difficulties in the implementation of digital hardware. The solution can be found while using an approximation of exponential functions by polynomials of the first order, that, however, violates the rigor accordance of the analytical model with characteristics of a real object. There are two practical approaches to synthesize algorithms for control of hybrid systems. The first approach is based on the representation of the whole system by a discrete model which is described by difference equations that makes it possible to synthesize discrete algorithms. The second approach is based on description of the system by differential equations. The equations describe synthesis of continuous algorithms and their further implementation in a digital computer included in the control loop system. The paper considers modeling of a hybrid electrical engineering system using differential equations. Neglecting the pulse duration, it has been proposed to describe behavior of vector components in phase coordinates of the hybrid system by stochastic differential equations containing generally non-linear differentiable random functions. A stochastic vector-matrix equation describing dynamics of the

  16. Macromolecular structure determination in the post-genome era

    CERN Document Server

    Kuhn, P

    2001-01-01

    Recent advances in genetics, molecular biology and crystallographic instrumentation and methodology have led to a revolution in the field of Structural Molecular Biology (SMB). These combined advances have paved the way to a more complete and detailed understanding of the biological macromolecules that make up an organism, both in terms of their individual functions and also the interactions between them. In this paper we describe a large-scale, genomic approach to the three-dimensional structure determination of macromolecules and their complexes, using high-throughput methodology to streamline all aspects of the process. This task requires the development of automated high-intensity synchrotron beam lines for X-ray diffraction data collection from single crystal samples. Furthermore, these beam lines must be operated within a sophisticated software and hardware environment, which is capable of delivering a completely automated structure determination pipeline. The SMB resource at SSRL is developing a system...

  17. Oxygen production System Models for Lunar ISRU

    Science.gov (United States)

    Santiago-Maldonado, Edgardo

    2007-01-01

    In-Situ Resource Utilization (ISRU) seeks to make human space exploration feasible; by using available resources from a planet or the moon to produce consumables, parts, and structures that otherwise would be brought from Earth. Producing these in situ reduces the mass of such that must be launched and doing so allows more payload mass' for each mission. The production of oxygen from lunar regolith, for life support and propellant, is one of the tasks being studied under ISRU. NASA is currently funding three processes that have shown technical merit for the production of oxygen from regolith: Molten Salt Electrolysis, Hydrogen Reduction of Ilmenite, and Carbothermal Reduction. The ISRU program is currently developing system models of, the , abovementioned processes to: (1) help NASA in the evaluation process to select the most cost-effective and efficient process for further prototype development, (2) identify key parameters, (3) optimize the oxygen production process, (4) provide estimates on energy and power requirements, mass and volume.of the system, oxygen production rate, mass of regolith required, mass of consumables, and other important parameters, and (5) integrate into the overall end-to-end ISRU system model, which could be integrated with mission architecture models. The oxygen production system model is divided into modules that represent unit operations (e.g., reactor, water electrolyzer, heat exchanger). Each module is modeled theoretically using Excel and Visual Basic for Applications (VBA), and will be validated using experimental data from on-going laboratory work. This modularity (plug-n-play) feature of each unit operation allows the use of the same model on different oxygen production systems simulations resulting in comparable results. In this presentation, preliminary results for mass, power, volume will be presented along with brief description of the oxygen production system model.

  18. The complex portal--an encyclopaedia of macromolecular complexes.

    Science.gov (United States)

    Meldal, Birgit H M; Forner-Martinez, Oscar; Costanzo, Maria C; Dana, Jose; Demeter, Janos; Dumousseau, Marine; Dwight, Selina S; Gaulton, Anna; Licata, Luana; Melidoni, Anna N; Ricard-Blum, Sylvie; Roechert, Bernd; Skyzypek, Marek S; Tiwari, Manu; Velankar, Sameer; Wong, Edith D; Hermjakob, Henning; Orchard, Sandra

    2015-01-01

    The IntAct molecular interaction database has created a new, free, open-source, manually curated resource, the Complex Portal (www.ebi.ac.uk/intact/complex), through which protein complexes from major model organisms are being collated and made available for search, viewing and download. It has been built in close collaboration with other bioinformatics services and populated with data from ChEMBL, MatrixDB, PDBe, Reactome and UniProtKB. Each entry contains information about the participating molecules (including small molecules and nucleic acids), their stoichiometry, topology and structural assembly. Complexes are annotated with details about their function, properties and complex-specific Gene Ontology (GO) terms. Consistent nomenclature is used throughout the resource with systematic names, recommended names and a list of synonyms all provided. The use of the Evidence Code Ontology allows us to indicate for which entries direct experimental evidence is available or if the complex has been inferred based on homology or orthology. The data are searchable using standard identifiers, such as UniProt, ChEBI and GO IDs, protein, gene and complex names or synonyms. This reference resource will be maintained and grow to encompass an increasing number of organisms. Input from groups and individuals with specific areas of expertise is welcome. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Operation of the Australian Store.Synchrotron for macromolecular crystallography

    International Nuclear Information System (INIS)

    Meyer, Grischa R.; Aragão, David; Mudie, Nathan J.; Caradoc-Davies, Tom T.; McGowan, Sheena; Bertling, Philip J.; Groenewegen, David; Quenette, Stevan M.; Bond, Charles S.; Buckle, Ashley M.; Androulakis, Steve

    2014-01-01

    The Store.Synchrotron service, a fully functional, cloud computing-based solution to raw X-ray data archiving and dissemination at the Australian Synchrotron, is described. The Store.Synchrotron service, a fully functional, cloud computing-based solution to raw X-ray data archiving and dissemination at the Australian Synchrotron, is described. The service automatically receives and archives raw diffraction data, related metadata and preliminary results of automated data-processing workflows. Data are able to be shared with collaborators and opened to the public. In the nine months since its deployment in August 2013, the service has handled over 22.4 TB of raw data (∼1.7 million diffraction images). Several real examples from the Australian crystallographic community are described that illustrate the advantages of the approach, which include real-time online data access and fully redundant, secure storage. Discoveries in biological sciences increasingly require multidisciplinary approaches. With this in mind, Store.Synchrotron has been developed as a component within a greater service that can combine data from other instruments at the Australian Synchrotron, as well as instruments at the Australian neutron source ANSTO. It is therefore envisaged that this will serve as a model implementation of raw data archiving and dissemination within the structural biology research community

  20. Qualitative models for space system engineering

    Science.gov (United States)

    Forbus, Kenneth D.

    1990-01-01

    The objectives of this project were: (1) to investigate the implications of qualitative modeling techniques for problems arising in the monitoring, diagnosis, and design of Space Station subsystems and procedures; (2) to identify the issues involved in using qualitative models to enhance and automate engineering functions. These issues include representing operational criteria, fault models, alternate ontologies, and modeling continuous signals at a functional level of description; and (3) to develop a prototype collection of qualitative models for fluid and thermal systems commonly found in Space Station subsystems. Potential applications of qualitative modeling to space-systems engineering, including the notion of intelligent computer-aided engineering are summarized. Emphasis is given to determining which systems of the proposed Space Station provide the most leverage for study, given the current state of the art. Progress on using qualitative models, including development of the molecular collection ontology for reasoning about fluids, the interaction of qualitative and quantitative knowledge in analyzing thermodynamic cycles, and an experiment on building a natural language interface to qualitative reasoning is reported. Finally, some recommendations are made for future research.

  1. LOKI: a practical modelling and support system for telepresence systems

    International Nuclear Information System (INIS)

    Griffin, M.; Bridgewater, C.E.

    1993-01-01

    The use of Virtual Reality headset systems, in combination with a tele-presence ''head'' is discussed. The system is attached to a Unimate Puma robot arm and manipulated by the operator, using information gathered by the camera and auditory system, displayed via the Virtual Reality helmet. Operator commands are cross checked by using a modelling system, held on the Virtual Reality system. This system was found to supply a good sense of spacial awareness of the robot's domain. Actions which might move the robot outside its suitable operating envelope, or create a collision with the environment, were successfully blocked. This approach is seen as useful within the area of tele-operation. (author)

  2. The collection of MicroED data for macromolecular crystallography.

    Science.gov (United States)

    Shi, Dan; Nannenga, Brent L; de la Cruz, M Jason; Liu, Jinyang; Sawtelle, Steven; Calero, Guillermo; Reyes, Francis E; Hattne, Johan; Gonen, Tamir

    2016-05-01

    The formation of large, well-ordered crystals for crystallographic experiments remains a crucial bottleneck to the structural understanding of many important biological systems. To help alleviate this problem in crystallography, we have developed the MicroED method for the collection of electron diffraction data from 3D microcrystals and nanocrystals of radiation-sensitive biological material. In this approach, liquid solutions containing protein microcrystals are deposited on carbon-coated electron microscopy grids and are vitrified by plunging them into liquid ethane. MicroED data are collected for each selected crystal using cryo-electron microscopy, in which the crystal is diffracted using very few electrons as the stage is continuously rotated. This protocol gives advice on how to identify microcrystals by light microscopy or by negative-stain electron microscopy in samples obtained from standard protein crystallization experiments. The protocol also includes information about custom-designed equipment for controlling crystal rotation and software for recording experimental parameters in diffraction image metadata. Identifying microcrystals, preparing samples and setting up the microscope for diffraction data collection take approximately half an hour for each step. Screening microcrystals for quality diffraction takes roughly an hour, and the collection of a single data set is ∼10 min in duration. Complete data sets and resulting high-resolution structures can be obtained from a single crystal or by merging data from multiple crystals.

  3. Modeling and Control of Underwater Robotic Systems

    Energy Technology Data Exchange (ETDEWEB)

    Schjoelberg, I:

    1996-12-31

    This doctoral thesis describes modeling and control of underwater vehicle-manipulator systems. The thesis also presents a model and a control scheme for a system consisting of a surface vessel connected to an underwater robotic system by means of a slender marine structure. The equations of motion of the underwater vehicle and manipulator are described and the system kinematics and properties presented. Feedback linearization technique is applied to the system and evaluated through a simulation study. Passivity-based controllers for vehicle and manipulator control are presented. Stability of the closed loop system is proved and simulation results are given. The equation of motion for lateral motion of a cable/riser system connected to a surface vessel at the top end and to a thruster at the bottom end is described and stability analysis and simulations are presented. The equations of motion in 3 degrees of freedom of the cable/riser, surface vessel and robotic system are given. Stability analysis of the total system with PD-controllers is presented. 47 refs., 32 figs., 7 tabs.

  4. Modeling and simulation of blood collection systems.

    Science.gov (United States)

    Alfonso, Edgar; Xie, Xiaolan; Augusto, Vincent; Garraud, Olivier

    2012-03-01

    This paper addresses the modeling and simulation of blood collection systems in France for both fixed site and mobile blood collection with walk in whole blood donors and scheduled plasma and platelet donors. Petri net models are first proposed to precisely describe different blood collection processes, donor behaviors, their material/human resource requirements and relevant regulations. Petri net models are then enriched with quantitative modeling of donor arrivals, donor behaviors, activity times and resource capacity. Relevant performance indicators are defined. The resulting simulation models can be straightforwardly implemented with any simulation language. Numerical experiments are performed to show how the simulation models can be used to select, for different walk in donor arrival patterns, appropriate human resource planning and donor appointment strategies.

  5. Modeling and Simulation Tools: From Systems Biology to Systems Medicine.

    Science.gov (United States)

    Olivier, Brett G; Swat, Maciej J; Moné, Martijn J

    2016-01-01

    Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools.

  6. Functional Modeling for Monitoring of Robotic System

    DEFF Research Database (Denmark)

    Wu, Haiyan; Bateman, Rikke R.; Zhang, Xinxin

    2018-01-01

    supervisors or cooperators. In this work, we focus on developing a modeling framework for monitoring robotic system based on means-end analysis and the concept of action phases from action theory. A circular cascaded action phase structure is proposed for building the model of cyclical robotic events......With the expansion of robotic applications in the industrial domain, it is important that the robots can execute their tasks in a safe and reliable way. A monitoring system can be implemented to ensure the detection of abnormal situations of the robots and report the abnormality to their human....... This functional model provide a formal way of decompose robotic tasks and analyze each level of conditions for an action to be executed successfully. It can be used for monitoring robotic systems by checking the preconditions in the action phases and identifying the failure modes. The proposed method...

  7. Modelling and Analysing Socio-Technical Systems

    DEFF Research Database (Denmark)

    Aslanyan, Zaruhi; Ivanova, Marieta Georgieva; Nielson, Flemming

    2015-01-01

    Modern organisations are complex, socio-technical systems consisting of a mixture of physical infrastructure, human actors, policies and processes. An in-creasing number of attacks on these organisations exploits vulnerabilities on all different levels, for example combining a malware attack...... with social engineering. Due to this combination of attack steps on technical and social levels, risk assessment in socio-technical systems is complex. Therefore, established risk assessment methods often abstract away the internal structure of an organisation and ignore human factors when modelling...... and assessing attacks. In our work we model all relevant levels of socio-technical systems, and propose evaluation techniques for analysing the security properties of the model. Our approach simplifies the identification of possible attacks and provides qualified assessment and ranking of attacks based...

  8. The Red Sea Modeling and Forecasting System

    KAUST Repository

    Hoteit, Ibrahim

    2015-04-01

    Despite its importance for a variety of socio-economical and political reasons and the presence of extensive coral reef gardens along its shores, the Red Sea remains one of the most under-studied large marine physical and biological systems in the global ocean. This contribution will present our efforts to build advanced modeling and forecasting capabilities for the Red Sea, which is part of the newly established Saudi ARAMCO Marine Environmental Research Center at KAUST (SAMERCK). Our Red Sea modeling system compromises both regional and nested costal MIT general circulation models (MITgcm) with resolutions varying between 8 km and 250 m to simulate the general circulation and mesoscale dynamics at various spatial scales, a 10-km resolution Weather Research Forecasting (WRF) model to simulate the atmospheric conditions, a 4-km resolution European Regional Seas Ecosystem Model (ERSEM) to simulate the Red Sea ecosystem, and a 1-km resolution WAVEWATCH-III model to simulate the wind driven surface waves conditions. We have also implemented an oil spill model, and a probabilistic dispersion and larval connectivity modeling system (CMS) based on a stochastic Lagrangian framework and incorporating biological attributes. We are using the models outputs together with available observational data to study all aspects of the Red Sea circulations. Advanced monitoring capabilities are being deployed in the Red Sea as part of the SAMERCK, comprising multiple gliders equipped with hydrographical and biological sensors, high frequency (HF) surface current/wave mapping, buoys/ moorings, etc, complementing the available satellite ocean and atmospheric observations and Automatic Weather Stations (AWS). The Red Sea models have also been equipped with advanced data assimilation capabilities. Fully parallel ensemble-based Kalman filtering (EnKF) algorithms have been implemented with the MITgcm and ERSEM for assimilating all available multivariate satellite and in-situ data sets. We

  9. Polyelectrolyte-mediated bridging interactions: columnar macromolecular phases

    International Nuclear Information System (INIS)

    Licer, Matjaz; Podgornik, Rudolf

    2010-01-01

    We present a mean-field theory for charged polymer chains in an external electrostatic field in the weak and strong coupling limits. We apply the theory to describe the statistical mechanics of flexible polyelectrolyte chains in a hexagonal columnar lattice of stiff cylindrical macroions, such as DNA, in a bathing solution of a uni-univalent salt (e.g. NaCl). The salt effects are first described in the Debye-Hueckel framework. This yields the macroion electrostatic field in the screened Coulomb form, which we take to represent the mean field into which the chains are immersed. We introduce the Green's function for the polyelectrolyte chains and derive the corresponding Edwards equation which we solve numerically in the Wigner-Seitz cylindrical cell using the ground state dominance ansatz. The solutions indicate the presence of polyelectrolyte bridging, which results in a like-charge attraction between stiff macroions. Then we reformulate the Edwards theory for the strong coupling case and use the standard Poisson-Boltzmann picture to describe the salt solution. We begin with the free energy which we minimize to obtain the Euler-Lagrange equations. The solutions yield self-consistently determined monomer density and electrostatic fields. We furthermore calculate the free energy density as well as the total osmotic pressure in the system. We again show that bridging implicates like-charge attractions of entropic origin between stiff cylindrical macroions. By analyzing the osmotic pressure we demonstrate that, in certain parts of the parameter space, a phase transition occurs between two phases of the same hexagonal symmetry.

  10. Recovering a Representative Conformational Ensemble from Underdetermined Macromolecular Structural Data

    Science.gov (United States)

    Berlin, Konstantin; Castañeda, Carlos A.; Schneidman-Duhovny, Dina; Sali, Andrej; Nava-Tudela, Alfredo; Fushman, David

    2013-01-01

    Structural analysis of proteins and nucleic acids is complicated by their inherent flexibility, conferred, for example, by linkers between their contiguous domains. Therefore, the macromolecule needs to be represented by an ensemble of conformations instead of a single conformation. Determining this ensemble is challenging because the experimental data are a convoluted average of contributions from multiple conformations. As the number of the ensemble degrees of freedom generally greatly exceeds the number of independent observables, directly deconvolving experimental data into a representative ensemble is an ill-posed problem. Recent developments in sparse approximations and compressive sensing have demonstrated that useful information can be recovered from underdetermined (ill-posed) systems of linear equations by using sparsity regularization. Inspired by these advances, we designed Sparse Ensemble Selection (SES) method for recovering multiple conformations from a limited number of observations. SES is more general and accurate than previously published minimum-ensemble methods, and we use it to obtain representative conformational ensembles of Lys48-linked di-ubiquitin, characterized by the residual dipolar coupling data measured at several pH conditions. These representative ensembles are validated against NMR chemical shift perturbation data and compared to maximum-entropy results. The SES method reproduced and quantified the previously observed pH dependence of the major conformation of Lys48-linked di-ubiquitin, and revealed lesser-populated conformations that are pre-organized for binding known di-ubiquitin receptors, thus providing insights into possible mechanisms of receptor recognition by polyubiquitin. SES is applicable to any experimental observables that can be expressed as a weighted linear combination of data for individual states. PMID:24093873

  11. Spatial Database Modeling for Indoor Navigation Systems

    Science.gov (United States)

    Gotlib, Dariusz; Gnat, Miłosz

    2013-12-01

    For many years, cartographers are involved in designing GIS and navigation systems. Most GIS applications use the outdoor data. Increasingly, similar applications are used inside buildings. Therefore it is important to find the proper model of indoor spatial database. The development of indoor navigation systems should utilize advanced teleinformation, geoinformatics, geodetic and cartographical knowledge. The authors present the fundamental requirements for the indoor data model for navigation purposes. Presenting some of the solutions adopted in the world they emphasize that navigation applications require specific data to present the navigation routes in the right way. There is presented original solution for indoor data model created by authors on the basis of BISDM model. Its purpose is to expand the opportunities for use in indoor navigation.

  12. Integrated Model of Bioenergy and Agriculture System

    DEFF Research Database (Denmark)

    Sigurjonsson, Hafthor Ægir; Elmegaard, Brian; Clausen, Lasse Røngaard

    2015-01-01

    approach that builds on Life Cycle Inventory and carries out Life Cycle Impact Assessment for a con- sequential Life Cycle Assessment on integrated bioenergy and agriculture systems. The model framework is built in Python which connects various freely available soft- ware that handle different aspects......Due to increased burden on the environment caused by human activities, focus on industrial ecology designs are gaining more attention. In that perspective an environ- mentally effective integration of bionergy and agriculture systems has significant potential. This work introduces a modeling...... of the overall model. C- TOOL and Yasso07 are used in the carbon balance of agri- culture, Dynamic Network Analysis is used for the energy simulation and Brightway2 is used to build a Life Cycle Inventory compatible database and processes it for vari- ous impacts assessment methods. The model is success- fully...

  13. Infectious disease modeling a hybrid system approach

    CERN Document Server

    Liu, Xinzhi

    2017-01-01

    This volume presents infectious diseases modeled mathematically, taking seasonality and changes in population behavior into account, using a switched and hybrid systems framework. The scope of coverage includes background on mathematical epidemiology, including classical formulations and results; a motivation for seasonal effects and changes in population behavior, an investigation into term-time forced epidemic models with switching parameters, and a detailed account of several different control strategies. The main goal is to study these models theoretically and to establish conditions under which eradication or persistence of the disease is guaranteed. In doing so, the long-term behavior of the models is determined through mathematical techniques from switched systems theory. Numerical simulations are also given to augment and illustrate the theoretical results and to help study the efficacy of the control schemes.

  14. Executable UML Modeling For Automotive Embedded Systems

    International Nuclear Information System (INIS)

    Gerard, Sebastien

    2000-01-01

    Engineers are more and more faced to the hard problem of sophisticated real-time System whereas time to market becomes always smaller. Object oriented modeling supported by UML standard brings effective solutions to such problems. However the possibility to specify real-time aspects of an application are not yet fully satisfactory Indeed, existing industrial proposals supply good answers to concurrency specification problem but they are yet limited regarding to real-time quantitative properties specification of an application. This work aims to construct a complete and consistent UML methodology based on a profile dedicated to automotive embedded Systems modeling and prototyping. This profile contains ail needed extensions to express easily the real-time quantitative properties of an application. Moreover, thanks to the formalization of UML protocol state machines, real-time concepts have been well-integrated in the object oriented paradigm. The main result of this deep integration is that a user is now able to model real-time Systems through the classical object oriented view i.e. without needing any specific knowing in real-time area. In order to answer to an industrial requirement, Systems prototyping (key point for car industry) the ACCORD/UML approach allows also to build executable models of an application. For that purpose, the method supplies a set of rules allow.ng to remove UML ambiguous semantics points, to complete semantics variation points and then to obtain a complete and coherent global model of an application being executable. The work of UML extension and its using formalization realized all along this thesis supplied also a complete and non-ambiguous modeling framework for automotive electronics Systems development. This is also a base particularly well-suited to tackle other facets of the Systems development as automatic and optimized code generation, validation, simulation or tests. (author) [fr

  15. Modelling carbon emissions in electric systems

    International Nuclear Information System (INIS)

    Lau, E.T.; Yang, Q.; Forbes, A.B.; Wright, P.; Livina, V.N.

    2014-01-01

    Highlights: • We model carbon emissions in electric systems. • We estimate emissions in generated and consumed energy with UK carbon factors. • We model demand profiles with novel function based on hyperbolic tangents. • We study datasets of UK Elexon database, Brunel PV system and Irish SmartGrid. • We apply Ensemble Kalman Filter to forecast energy data in these case studies. - Abstract: We model energy consumption of network electricity and compute Carbon emissions (CE) based on obtained energy data. We review various models of electricity consumption and propose an adaptive seasonal model based on the Hyperbolic tangent function (HTF). We incorporate HTF to define seasonal and daily trends of electricity demand. We then build a stochastic model that combines the trends and white noise component and the resulting simulations are estimated using Ensemble Kalman Filter (EnKF), which provides ensemble simulations of groups of electricity consumers; similarly, we estimate carbon emissions from electricity generators. Three case studies of electricity generation and consumption are modelled: Brunel University photovoltaic generation data, Elexon national electricity generation data (various fuel types) and Irish smart grid data, with ensemble estimations by EnKF and computation of carbon emissions. We show the flexibility of HTF-based functions for modelling realistic cycles of energy consumption, the efficiency of EnKF in ensemble estimation of energy consumption and generation, and report the obtained estimates of the carbon emissions in the considered case studies

  16. Fujisaki Model Based Intonation Modeling for Korean TTS System

    Science.gov (United States)

    Kim, Byeongchang; Lee, Jinsik; Lee, Gary Geunbae

    One of the enduring problems in developing high-quality TTS (text-to-speech) system is pitch contour generation. Considering language specific knowledge, an adjusted Fujisaki model for Korean TTS system is introduced along with refined machine learning features. The results of quantitative and qualitative evaluations show the validity of our system: the accuracy of the phrase command prediction is 0.8928; the correlations of the predicted amplitudes of a phrase command and an accent command are 0.6644 and 0.6002, respectively; our method achieved the level of "fair" naturalness (3.6) in a MOS scale for generated F0 curves.

  17. Complex Systems and Self-organization Modelling

    CERN Document Server

    Bertelle, Cyrille; Kadri-Dahmani, Hakima

    2009-01-01

    The concern of this book is the use of emergent computing and self-organization modelling within various applications of complex systems. The authors focus their attention both on the innovative concepts and implementations in order to model self-organizations, but also on the relevant applicative domains in which they can be used efficiently. This book is the outcome of a workshop meeting within ESM 2006 (Eurosis), held in Toulouse, France in October 2006.

  18. Agent-based models of cellular systems.

    Science.gov (United States)

    Cannata, Nicola; Corradini, Flavio; Merelli, Emanuela; Tesei, Luca

    2013-01-01

    Software agents are particularly suitable for engineering models and simulations of cellular systems. In a very natural and intuitive manner, individual software components are therein delegated to reproduce "in silico" the behavior of individual components of alive systems at a given level of resolution. Individuals' actions and interactions among individuals allow complex collective behavior to emerge. In this chapter we first introduce the readers to software agents and multi-agent systems, reviewing the evolution of agent-based modeling of biomolecular systems in the last decade. We then describe the main tools, platforms, and methodologies available for programming societies of agents, possibly profiting also of toolkits that do not require advanced programming skills.

  19. Modeling the Dynamic Digestive System Microbiome

    Directory of Open Access Journals (Sweden)

    Anne M. Estes

    2015-08-01

    Full Text Available “Modeling the Dynamic Digestive System Microbiome” is a hands-on activity designed to demonstrate the dynamics of microbiome ecology using dried pasta and beans to model disturbance events in the human digestive system microbiome. This exercise demonstrates how microbiome diversity is influenced by: 1 niche availability and habitat space and 2 a major disturbance event, such as antibiotic use. Students use a pictorial key to examine prepared models of digestive system microbiomes to determine what the person with the microbiome “ate.” Students then model the effect of taking antibiotics by removing certain “antibiotic sensitive” pasta. Finally, they add in “environmental microbes” or “native microbes” to recolonize the digestive system, determine how resilient their model microbome community is to disturbance, and discuss the implications. Throughout the exercise, students discuss differences in the habitat space available and microbiome community diversity. This exercise can be modified to discuss changes in the microbiome due to diet shifts and the emergence of antibiotic resistance in more depth.

  20. Model-based testing for embedded systems

    CERN Document Server

    Zander, Justyna; Mosterman, Pieter J

    2011-01-01

    What the experts have to say about Model-Based Testing for Embedded Systems: "This book is exactly what is needed at the exact right time in this fast-growing area. From its beginnings over 10 years ago of deriving tests from UML statecharts, model-based testing has matured into a topic with both breadth and depth. Testing embedded systems is a natural application of MBT, and this book hits the nail exactly on the head. Numerous topics are presented clearly, thoroughly, and concisely in this cutting-edge book. The authors are world-class leading experts in this area and teach us well-used

  1. The PQUAL Open System Quality Model

    Directory of Open Access Journals (Sweden)

    Cristian IONITA

    2012-01-01

    Full Text Available Quality assessment of open business enterprise systems is very important because those plat-forms play a central role in the organizations that implement them. The current paper proposes a new easily applicable software quality model called PQUAL that evaluates the quality of such systems. The quality characteristics are identified and analyzed using the ISO/IEC 9126 international standard as a starting point. The paper develops metrics to measure the quality level for the characteristics. The PQUAL model is applied to compare the quality of the DocuMentor and YAWL platforms.

  2. Business Models for Power System Flexibility

    DEFF Research Database (Denmark)

    Boscan, Luis; Poudineh, Rahmatallah

    2016-01-01

    As intermittent, renewable resources gain more share in the generation mix, the need for power system flexibility increases more than ever. Parallel to this, technological change and the emergence of new players bringing about innovative solutions are boosting the development of flexibility......-enabling business models, adding new activities to the existing supply chain. Ranging from technological to market-based innovation, this chapter reviews the latest developments in these emerging models. The main conclusion is that when flexibility becomes scarce in the system, new players with their innovative...

  3. Understanding and Modeling Teams As Dynamical Systems

    Directory of Open Access Journals (Sweden)

    Jamie C. Gorman

    2017-07-01

    Full Text Available By its very nature, much of teamwork is distributed across, and not stored within, interdependent people working toward a common goal. In this light, we advocate a systems perspective on teamwork that is based on general coordination principles that are not limited to cognitive, motor, and physiological levels of explanation within the individual. In this article, we present a framework for understanding and modeling teams as dynamical systems and review our empirical findings on teams as dynamical systems. We proceed by (a considering the question of why study teams as dynamical systems, (b considering the meaning of dynamical systems concepts (attractors; perturbation; synchronization; fractals in the context of teams, (c describe empirical studies of team coordination dynamics at the perceptual-motor, cognitive-behavioral, and cognitive-neurophysiological levels of analysis, and (d consider the theoretical and practical implications of this approach, including new kinds of explanations of human performance and real-time analysis and performance modeling. Throughout our discussion of the topics we consider how to describe teamwork using equations and/or modeling techniques that describe the dynamics. Finally, we consider what dynamical equations and models do and do not tell us about human performance in teams and suggest future research directions in this area.

  4. A multiscale modeling approach for biomolecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Bowling, Alan, E-mail: bowling@uta.edu; Haghshenas-Jaryani, Mahdi, E-mail: mahdi.haghshenasjaryani@mavs.uta.edu [The University of Texas at Arlington, Department of Mechanical and Aerospace Engineering (United States)

    2015-04-15

    This paper presents a new multiscale molecular dynamic model for investigating the effects of external interactions, such as contact and impact, during stepping and docking of motor proteins and other biomolecular systems. The model retains the mass properties ensuring that the result satisfies Newton’s second law. This idea is presented using a simple particle model to facilitate discussion of the rigid body model; however, the particle model does provide insights into particle dynamics at the nanoscale. The resulting three-dimensional model predicts a significant decrease in the effect of the random forces associated with Brownian motion. This conclusion runs contrary to the widely accepted notion that the motor protein’s movements are primarily the result of thermal effects. This work focuses on the mechanical aspects of protein locomotion; the effect ATP hydrolysis is estimated as internal forces acting on the mechanical model. In addition, the proposed model can be numerically integrated in a reasonable amount of time. Herein, the differences between the motion predicted by the old and new modeling approaches are compared using a simplified model of myosin V.

  5. Energy Systems Modelling Research and Analysis

    DEFF Research Database (Denmark)

    Møller Andersen, Frits; Alberg Østergaard, Poul

    2015-01-01

    This editorial introduces the seventh volume of the International Journal of Sustainable Energy Planning and Management. The volume presents part of the outcome of the project Energy Systems Modelling Research and Analysis (ENSYMORA) funded by the Danish Innovation Fund. The project carried out...... by 11 university and industry partners has improved the basis for decision-making within energy planning and energy scenario making by providing new and improved tools and methods for energy systems analyses....

  6. Automated Qualitative Modeling of Dynamic Physical Systems

    Science.gov (United States)

    1993-01-01

    Resnick, Naomi Ribner, Ruth Schonfeld, Re- becca Simmons, Cindy Wible, and especially David Clemens, Nomi Harris, Michele Popper , Karen Sarachik, and...describe a part of a system by using a component name, such as "mo- tor." MM accepts both geometric and component descriptions, and allows t, e two...not a scientific discovery program along the lines of, say, BACON [201, which could also be said to be constructing models of systems. Thus the first

  7. Drinking Water Temperature Modelling in Domestic Systems

    OpenAIRE

    Moerman, A.; Blokker, M.; Vreeburg, J.; van der Hoek, J.P.

    2014-01-01

    Domestic water supply systems are the final stage of the transport process to deliver potable water to the customers’ tap. Under the influence of temperature, residence time and pipe materials the drinking water quality can change while the water passes the domestic drinking water system. According to the Dutch Drinking Water Act the drinking water temperature may not exceed the 25 °C threshold at point-of-use level. This paper provides a mathematical approach to model the heating of drinking...

  8. Improvements in continuum modeling for biomolecular systems

    Science.gov (United States)

    Yu, Qiao; Ben-Zhuo, Lu

    2016-01-01

    Modeling of biomolecular systems plays an essential role in understanding biological processes, such as ionic flow across channels, protein modification or interaction, and cell signaling. The continuum model described by the Poisson- Boltzmann (PB)/Poisson-Nernst-Planck (PNP) equations has made great contributions towards simulation of these processes. However, the model has shortcomings in its commonly used form and cannot capture (or cannot accurately capture) some important physical properties of the biological systems. Considerable efforts have been made to improve the continuum model to account for discrete particle interactions and to make progress in numerical methods to provide accurate and efficient simulations. This review will summarize recent main improvements in continuum modeling for biomolecular systems, with focus on the size-modified models, the coupling of the classical density functional theory and the PNP equations, the coupling of polar and nonpolar interactions, and numerical progress. Project supported by the National Natural Science Foundation of China (Grant No. 91230106) and the Chinese Academy of Sciences Program for Cross & Cooperative Team of the Science & Technology Innovation.

  9. System of systems dependability – Theoretical models and applications examples

    International Nuclear Information System (INIS)

    Bukowski, L.

    2016-01-01

    The aim of this article is to generalise the concept of "dependability" in a way, that could be applied to all types of systems, especially the system of systems (SoS), operating under both normal and abnormal work conditions. In order to quantitatively assess the dependability we applied service continuity oriented approach. This approach is based on the methodology of service engineering and is closely related to the idea of resilient enterprise as well as to the concept of disruption-tolerant operation. On this basis a framework for evaluation of SoS dependability has been developed in a static as well as dynamic approach. The static model is created as a fuzzy logic-oriented advisory expert system and can be particularly useful at the design stage of SoS. The dynamic model is based on the risk oriented approach, and can be useful both at the design stage and for management of SoS. The integrated model of dependability can also form the basis for a new definition of the dependability engineering, namely as a superior discipline to reliability engineering, safety engineering, security engineering, resilience engineering and risk engineering. - Highlights: • A framework for evaluation of system of systems dependability is presented. • The model is based on the service continuity concept and consists of two parts. • The static part can be created as a fuzzy logic-oriented advisory expert system. • The dynamic, risk oriented part, is related to the concept of throughput chain. • A new definition of dependability engineering is proposed.

  10. Modeling leaks from liquid hydrogen storage systems.

    Energy Technology Data Exchange (ETDEWEB)

    Winters, William Stanley, Jr.

    2009-01-01

    This report documents a series of models for describing intended and unintended discharges from liquid hydrogen storage systems. Typically these systems store hydrogen in the saturated state at approximately five to ten atmospheres. Some of models discussed here are equilibrium-based models that make use of the NIST thermodynamic models to specify the states of multiphase hydrogen and air-hydrogen mixtures. Two types of discharges are considered: slow leaks where hydrogen enters the ambient at atmospheric pressure and fast leaks where the hydrogen flow is usually choked and expands into the ambient through an underexpanded jet. In order to avoid the complexities of supersonic flow, a single Mach disk model is proposed for fast leaks that are choked. The velocity and state of hydrogen downstream of the Mach disk leads to a more tractable subsonic boundary condition. However, the hydrogen temperature exiting all leaks (fast or slow, from saturated liquid or saturated vapor) is approximately 20.4 K. At these temperatures, any entrained air would likely condense or even freeze leading to an air-hydrogen mixture that cannot be characterized by the REFPROP subroutines. For this reason a plug flow entrainment model is proposed to treat a short zone of initial entrainment and heating. The model predicts the quantity of entrained air required to bring the air-hydrogen mixture to a temperature of approximately 65 K at one atmosphere. At this temperature the mixture can be treated as a mixture of ideal gases and is much more amenable to modeling with Gaussian entrainment models and CFD codes. A Gaussian entrainment model is formulated to predict the trajectory and properties of a cold hydrogen jet leaking into ambient air. The model shows that similarity between two jets depends on the densimetric Froude number, density ratio and initial hydrogen concentration.

  11. Transforming Graphical System Models To Graphical Attack Models

    NARCIS (Netherlands)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, René Rydhof; Kammüller, Florian; Mauw, S.; Kordy, B.

    2015-01-01

    Manually identifying possible attacks on an organisation is a complex undertaking; many different factors must be considered, and the resulting attack scenarios can be complex and hard to maintain as the organisation changes. System models provide a systematic representation of organisations that

  12. Guideliness for system modeling: fault tree [analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Hwan; Yang, Joon Eon; Kang, Dae Il; Hwang, Mee Jeong

    2004-07-01

    This document, the guidelines for system modeling related to Fault Tree Analysis(FTA), is intended to provide the guidelines with the analyzer to construct the fault trees in the level of the capability category II of ASME PRA standard. Especially, they are to provide the essential and basic guidelines and the related contents to be used in support of revising the Ulchin 3 and 4 PSA model for risk monitor within the capability category II of ASME PRA standard. Normally the main objective of system analysis is to assess the reliability of system modeled by Event Tree Analysis (ETA). A variety of analytical techniques can be used for the system analysis, however, FTA method is used in this procedures guide. FTA is the method used for representing the failure logic of plant systems deductively using AND, OR or NOT gates. The fault tree should reflect all possible failure modes that may contribute to the system unavailability. This should include contributions due to the mechanical failures of the components, Common Cause Failures (CCFs), human errors and outages for testing and maintenance. This document identifies and describes the definitions and the general procedures of FTA and the essential and basic guidelines for reving the fault trees. Accordingly, the guidelines for FTA will be capable to guide the FTA to the level of the capability category II of ASME PRA standard.

  13. Modelling the crop: from system dynamics to systems biology

    NARCIS (Netherlands)

    Yin, X.; Struik, P.C.

    2010-01-01

    There is strong interplant competition in a crop stand for various limiting resources, resulting in complex compensation and regulation mechanisms along the developmental cascade of the whole crop. Despite decades-long use of principles in system dynamics (e.g. feedback control), current crop models

  14. The Launch Systems Operations Cost Model

    Science.gov (United States)

    Prince, Frank A.; Hamaker, Joseph W. (Technical Monitor)

    2001-01-01

    One of NASA's primary missions is to reduce the cost of access to space while simultaneously increasing safety. A key component, and one of the least understood, is the recurring operations and support cost for reusable launch systems. In order to predict these costs, NASA, under the leadership of the Independent Program Assessment Office (IPAO), has commissioned the development of a Launch Systems Operations Cost Model (LSOCM). LSOCM is a tool to predict the operations & support (O&S) cost of new and modified reusable (and partially reusable) launch systems. The requirements are to predict the non-recurring cost for the ground infrastructure and the recurring cost of maintaining that infrastructure, performing vehicle logistics, and performing the O&S actions to return the vehicle to flight. In addition, the model must estimate the time required to cycle the vehicle through all of the ground processing activities. The current version of LSOCM is an amalgamation of existing tools, leveraging our understanding of shuttle operations cost with a means of predicting how the maintenance burden will change as the vehicle becomes more aircraft like. The use of the Conceptual Operations Manpower Estimating Tool/Operations Cost Model (COMET/OCM) provides a solid point of departure based on shuttle and expendable launch vehicle (ELV) experience. The incorporation of the Reliability and Maintainability Analysis Tool (RMAT) as expressed by a set of response surface model equations gives a method for estimating how changing launch system characteristics affects cost and cycle time as compared to today's shuttle system. Plans are being made to improve the model. The development team will be spending the next few months devising a structured methodology that will enable verified and validated algorithms to give accurate cost estimates. To assist in this endeavor the LSOCM team is part of an Agency wide effort to combine resources with other cost and operations professionals to

  15. SYSTEMS MODELING OF PROSTATE REGULATION AND ...

    Science.gov (United States)

    The prostate is an androgen-dependent tissue that is an important site of disease in human males as well as an important indicator of androgen status in animals. The rat prostate is used for studying antiandrogenic drugs as well as for evaluation of endocrine disruption (e.g., Hershberger Assay). Pubertal changes in the prostate have been observed to be as sensitive to environmental antiandrogens as in utero effects. The goal of this research is to model the biology of prostate androgen function on a systems level to determine the factors responsible for the dose-response observable with androgens and antiandrogens in the male rat. This includes investigation of the roles of positive and negative feedback loops in prostatic response following castration and dosing with testosterone and/or antiandrogens. A biologically-based, systems-level model will be developed describing the regulation of the prostate by androgens. The model will extend an existing model for the male rat central axis, which describes feedback between luteinizing hormone and testosterone production in the testes, to include the prostate and conversion of testosterone to dihydrotestosterone (DHT). The prostate model will describe binding of androgens to the androgen receptor, 5α-reductase catalyzed production of DHT, and gene regulation affecting cell proliferation, apoptosis, and prostatic fluid production. The model will combine pharmacokinetic models for endogenous hormones (i.e., testost

  16. Cognitive Systems Modeling and Analysis of Command and Control Systems

    Science.gov (United States)

    Norlander, Arne

    2012-01-01

    Military operations, counter-terrorism operations and emergency response often oblige operators and commanders to operate within distributed organizations and systems for safe and effective mission accomplishment. Tactical commanders and operators frequently encounter violent threats and critical demands on cognitive capacity and reaction time. In the future they will make decisions in situations where operational and system characteristics are highly dynamic and non-linear, i.e. minor events, decisions or actions may have serious and irreversible consequences for the entire mission. Commanders and other decision makers must manage true real time properties at all levels; individual operators, stand-alone technical systems, higher-order integrated human-machine systems and joint operations forces alike. Coping with these conditions in performance assessment, system development and operational testing is a challenge for both practitioners and researchers. This paper reports on research from which the results led to a breakthrough: An integrated approach to information-centered systems analysis to support future command and control systems research development. This approach integrates several areas of research into a coherent framework, Action Control Theory (ACT). It comprises measurement techniques and methodological advances that facilitate a more accurate and deeper understanding of the operational environment, its agents, actors and effectors, generating new and updated models. This in turn generates theoretical advances. Some good examples of successful approaches are found in the research areas of cognitive systems engineering, systems theory, and psychophysiology, and in the fields of dynamic, distributed decision making and naturalistic decision making.

  17. Modelling water uptake efficiency of root systems

    Science.gov (United States)

    Leitner, Daniel; Tron, Stefania; Schröder, Natalie; Bodner, Gernot; Javaux, Mathieu; Vanderborght, Jan; Vereecken, Harry; Schnepf, Andrea

    2016-04-01

    Water uptake is crucial for plant productivity. Trait based breeding for more water efficient crops will enable a sustainable agricultural management under specific pedoclimatic conditions, and can increase drought resistance of plants. Mathematical modelling can be used to find suitable root system traits for better water uptake efficiency defined as amount of water taken up per unit of root biomass. This approach requires large simulation times and large number of simulation runs, since we test different root systems under different pedoclimatic conditions. In this work, we model water movement by the 1-dimensional Richards equation with the soil hydraulic properties described according to the van Genuchten model. Climatic conditions serve as the upper boundary condition. The root system grows during the simulation period and water uptake is calculated via a sink term (after Tron et al. 2015). The goal of this work is to compare different free software tools based on different numerical schemes to solve the model. We compare implementations using DUMUX (based on finite volumes), Hydrus 1D (based on finite elements), and a Matlab implementation of Van Dam, J. C., & Feddes 2000 (based on finite differences). We analyse the methods for accuracy, speed and flexibility. Using this model case study, we can clearly show the impact of various root system traits on water uptake efficiency. Furthermore, we can quantify frequent simplifications that are introduced in the modelling step like considering a static root system instead of a growing one, or considering a sink term based on root density instead of considering the full root hydraulic model (Javaux et al. 2008). References Tron, S., Bodner, G., Laio, F., Ridolfi, L., & Leitner, D. (2015). Can diversity in root architecture explain plant water use efficiency? A modeling study. Ecological modelling, 312, 200-210. Van Dam, J. C., & Feddes, R. A. (2000). Numerical simulation of infiltration, evaporation and shallow

  18. Bionic models for identification of biological systems

    Science.gov (United States)

    Gerget, O. M.

    2017-01-01

    This article proposes a clinical decision support system that processes biomedical data. For this purpose a bionic model has been designed based on neural networks, genetic algorithms and immune systems. The developed system has been tested on data from pregnant women. The paper focuses on the approach to enable selection of control actions that can minimize the risk of adverse outcome. The control actions (hyperparameters of a new type) are further used as an additional input signal. Its values are defined by a hyperparameter optimization method. A software developed with Python is briefly described.

  19. Statistical Model Checking for Biological Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Larsen, Kim Guldstrand; Legay, Axel

    2014-01-01

    Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfies a given linear temporal property. The technique has been applied to (discrete and continuous time) Markov chains, stochastic...... timed automata and most recently hybrid systems using the tool Uppaal SMC. In this paper we enable the application of SMC to complex biological systems, by combining Uppaal SMC with ANIMO, a plugin of the tool Cytoscape used by biologists, as well as with SimBiology®, a plugin of Matlab to simulate...

  20. Data Model Management for Space Information Systems

    Science.gov (United States)

    Hughes, J. Steven; Crichton, Daniel J.; Ramirez, Paul; Mattmann, chris

    2006-01-01

    The Reference Architecture for Space Information Management (RASIM) suggests the separation of the data model from software components to promote the development of flexible information management systems. RASIM allows the data model to evolve independently from the software components and results in a robust implementation that remains viable as the domain changes. However, the development and management of data models within RASIM are difficult and time consuming tasks involving the choice of a notation, the capture of the model, its validation for consistency, and the export of the model for implementation. Current limitations to this approach include the lack of ability to capture comprehensive domain knowledge, the loss of significant modeling information during implementation, the lack of model visualization and documentation capabilities, and exports being limited to one or two schema types. The advent of the Semantic Web and its demand for sophisticated data models has addressed this situation by providing a new level of data model management in the form of ontology tools. In this paper we describe the use of a representative ontology tool to capture and manage a data model for a space information system. The resulting ontology is implementation independent. Novel on-line visualization and documentation capabilities are available automatically, and the ability to export to various schemas can be added through tool plug-ins. In addition, the ingestion of data instances into the ontology allows validation of the ontology and results in a domain knowledge base. Semantic browsers are easily configured for the knowledge base. For example the export of the knowledge base to RDF/XML and RDFS/XML and the use of open source metadata browsers provide ready-made user interfaces that support both text- and facet-based search. This paper will present the Planetary Data System (PDS) data model as a use case and describe the import of the data model into an ontology tool

  1. Session 6: Dynamic Modeling and Systems Analysis

    Science.gov (United States)

    Csank, Jeffrey; Chapman, Jeffryes; May, Ryan

    2013-01-01

    These presentations cover some of the ongoing work in dynamic modeling and dynamic systems analysis. The first presentation discusses dynamic systems analysis and how to integrate dynamic performance information into the systems analysis. The ability to evaluate the dynamic performance of an engine design may allow tradeoffs between the dynamic performance and operability of a design resulting in a more efficient engine design. The second presentation discusses the Toolbox for Modeling and Analysis of Thermodynamic Systems (T-MATS). T-MATS is a Simulation system with a library containing the basic building blocks that can be used to create dynamic Thermodynamic Systems. Some of the key features include Turbo machinery components, such as turbines, compressors, etc., and basic control system blocks. T-MAT is written in the Matlab-Simulink environment and is open source software. The third presentation focuses on getting additional performance from the engine by allowing the limit regulators only to be active when a limit is danger of being violated. Typical aircraft engine control architecture is based on MINMAX scheme, which is designed to keep engine operating within prescribed mechanical/operational safety limits. Using a conditionally active min-max limit regulator scheme, additional performance can be gained by disabling non-relevant limit regulators

  2. Mars 2020 Model Based Systems Engineering Pilot

    Science.gov (United States)

    Dukes, Alexandra Marie

    2017-01-01

    The pilot study is led by the Integration Engineering group in NASA's Launch Services Program (LSP). The Integration Engineering (IE) group is responsible for managing the interfaces between the spacecraft and launch vehicle. This pilot investigates the utility of Model-Based Systems Engineering (MBSE) with respect to managing and verifying interface requirements. The main objectives of the pilot are to model several key aspects of the Mars 2020 integrated operations and interface requirements based on the design and verification artifacts from Mars Science Laboratory (MSL) and to demonstrate how MBSE could be used by LSP to gain further insight on the interface between the spacecraft and launch vehicle as well as to enhance how LSP manages the launch service. The method used to accomplish this pilot started through familiarization of SysML, MagicDraw, and the Mars 2020 and MSL systems through books, tutorials, and NASA documentation. MSL was chosen as the focus of the model since its processes and verifications translate easily to the Mars 2020 mission. The study was further focused by modeling specialized systems and processes within MSL in order to demonstrate the utility of MBSE for the rest of the mission. The systems chosen were the In-Flight Disconnect (IFD) system and the Mass Properties process. The IFD was chosen as a system of focus since it is an interface between the spacecraft and launch vehicle which can demonstrate the usefulness of MBSE from a system perspective. The Mass Properties process was chosen as a process of focus since the verifications for mass properties occur throughout the lifecycle and can demonstrate the usefulness of MBSE from a multi-discipline perspective. Several iterations of both perspectives have been modeled and evaluated. While the pilot study will continue for another 2 weeks, pros and cons of using MBSE for LSP IE have been identified. A pro of using MBSE includes an integrated view of the disciplines, requirements, and

  3. Model based control of refrigeration systems

    Energy Technology Data Exchange (ETDEWEB)

    Sloth Larsen, L.F.

    2005-11-15

    The subject for this Ph.D. thesis is model based control of refrigeration systems. Model based control covers a variety of different types of controls, that incorporates mathematical models. In this thesis the main subject therefore has been restricted to deal with system optimizing control. The optimizing control is divided into two layers, where the system oriented top layers deals with set-point optimizing control and the lower layer deals with dynamical optimizing control in the subsystems. The thesis has two main contributions, i.e. a novel approach for set-point optimization and a novel approach for desynchronization based on dynamical optimization. The focus in the development of the proposed set-point optimizing control has been on deriving a simple and general method, that with ease can be applied on various compositions of the same class of systems, such as refrigeration systems. The method is based on a set of parameter depended static equations describing the considered process. By adapting the parameters to the given process, predict the steady state and computing a steady state gradient of the cost function, the process can be driven continuously towards zero gradient, i.e. the optimum (if the cost function is convex). The method furthermore deals with system constrains by introducing barrier functions, hereby the best possible performance taking the given constrains in to account can be obtained, e.g. under extreme operational conditions. The proposed method has been applied on a test refrigeration system, placed at Aalborg University, for minimization of the energy consumption. Here it was proved that by using general static parameter depended system equations it was possible drive the set-points close to the optimum and thus reduce the power consumption with up to 20%. In the dynamical optimizing layer the idea is to optimize the operation of the subsystem or the groupings of subsystems, that limits the obtainable system performance. In systems

  4. Quantitative system validation in model driven design

    DEFF Research Database (Denmark)

    Hermanns, Hilger; Larsen, Kim Guldstrand; Raskin, Jean-Francois

    2010-01-01

    The European STREP project Quasimodo1 develops theory, techniques and tool components for handling quantitative constraints in model-driven development of real-time embedded systems, covering in particular real-time, hybrid and stochastic aspects. This tutorial highlights the advances made...

  5. Model Checking - Automated Verification of Computational Systems

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 7. Model Checking - Automated Verification of Computational Systems. Madhavan Mukund. General Article Volume 14 Issue 7 July 2009 pp 667-681. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Advances in Modelling, System Identification and Parameter ...

    Indian Academy of Sciences (India)

    models determined from flight test data by using parameter estimation methods find extensive use in design/modification of flight control systems, high fidelity flight simulators and evaluation of handling qualitites of aircraft and rotorcraft. R K Mehra et al present new algorithms and results for flutter tests and adaptive notching ...

  7. Packet models revisited: tandem and priority systems

    NARCIS (Netherlands)

    M.R.H. Mandjes (Michel)

    2004-01-01

    textabstractWe examine two extensions of traditional single-node packet-scale queueing models: tandem networks and (strict) priority systems. Two generic input processes are considered: periodic and Poisson arrivals. For the two-node tandem, an exact expression is derived for the joint distribution

  8. System identification application using Hammerstein model

    Indian Academy of Sciences (India)

    Saban Ozer

    . 20(1): 1175–1188. [4] Hizir N B, Phan M Q, Betti R and Longman R W 2012. Identification of discrete-time bilinear systems through equivalent linear models. Nonlinear Dyn. 69(4): 2065–2078. [5] Hong X, Mitchell R J, Chen S, Harris C J, Li K ...

  9. Cost effectiveness of recycling: A systems model

    Energy Technology Data Exchange (ETDEWEB)

    Tonjes, David J., E-mail: david.tonjes@stonybrook.edu [Department of Technology and Society, College of Engineering and Applied Sciences, Stony Brook University, Stony Brook, NY 11794-3560 (United States); Waste Reduction and Management Institute, School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY 11794-5000 (United States); Center for Bioenergy Research and Development, Advanced Energy Research and Technology Center, Stony Brook University, 1000 Innovation Rd., Stony Brook, NY 11794-6044 (United States); Mallikarjun, Sreekanth, E-mail: sreekanth.mallikarjun@stonybrook.edu [Department of Technology and Society, College of Engineering and Applied Sciences, Stony Brook University, Stony Brook, NY 11794-3560 (United States)

    2013-11-15

    Highlights: • Curbside collection of recyclables reduces overall system costs over a range of conditions. • When avoided costs for recyclables are large, even high collection costs are supported. • When avoided costs for recyclables are not great, there are reduced opportunities for savings. • For common waste compositions, maximizing curbside recyclables collection always saves money. - Abstract: Financial analytical models of waste management systems have often found that recycling costs exceed direct benefits, and in order to economically justify recycling activities, externalities such as household expenses or environmental impacts must be invoked. Certain more empirically based studies have also found that recycling is more expensive than disposal. Other work, both through models and surveys, have found differently. Here we present an empirical systems model, largely drawn from a suburban Long Island municipality. The model accounts for changes in distribution of effort as recycling tonnages displace disposal tonnages, and the seven different cases examined all show that curbside collection programs that manage up to between 31% and 37% of the waste stream should result in overall system savings. These savings accrue partially because of assumed cost differences in tip fees for recyclables and disposed wastes, and also because recycling can result in a more efficient, cost-effective collection program. These results imply that increases in recycling are justifiable due to cost-savings alone, not on more difficult to measure factors that may not impact program budgets.

  10. Temperature Calculations in the Coastal Modeling System

    Science.gov (United States)

    2017-04-01

    with the change of water turbidity in coastal and estuarine systems. Water quality and ecological models often require input of water temperature...of the American Society of Civil Engineers 81(717): 1–11. Sánchez, A., W. Wu, H. Li, M. E. Brown, C. W. Reed, J. D. Rosati, and Z. Demirbilek. 2014

  11. Modelling Web-Based Instructional Systems

    NARCIS (Netherlands)

    Retalis, Symeon; Avgeriou, Paris

    2002-01-01

    The size and complexity of modern instructional systems, which are based on the World Wide Web, bring about great intricacy in their crafting, as there is not enough knowledge or experience in this field. This imposes the use of new instructional design models in order to achieve risk-mitigation,

  12. Control Architecture Modeling for Future Power Systems

    DEFF Research Database (Denmark)

    Heussen, Kai

    and operation structures; and finally the application to some concrete study cases, including a present system balancing, and proposed control structures such as Microgrids and Cells. In the second part, the main contributions are the outline of a formation strategy, integrating the design and model...

  13. ECONOMIC AND MATHEMATICAL MODELING INNOVATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    D.V. Makarov

    2014-06-01

    Full Text Available The paper presents one of the mathematical tools for modeling innovation processes. With the help of Kondratieff long waves can define innovation cycles. However, complexity of the innovation system implies a qualitative description. The article describes the problems of this area of research.

  14. Cost effectiveness of recycling: A systems model

    International Nuclear Information System (INIS)

    Tonjes, David J.; Mallikarjun, Sreekanth

    2013-01-01

    Highlights: • Curbside collection of recyclables reduces overall system costs over a range of conditions. • When avoided costs for recyclables are large, even high collection costs are supported. • When avoided costs for recyclables are not great, there are reduced opportunities for savings. • For common waste compositions, maximizing curbside recyclables collection always saves money. - Abstract: Financial analytical models of waste management systems have often found that recycling costs exceed direct benefits, and in order to economically justify recycling activities, externalities such as household expenses or environmental impacts must be invoked. Certain more empirically based studies have also found that recycling is more expensive than disposal. Other work, both through models and surveys, have found differently. Here we present an empirical systems model, largely drawn from a suburban Long Island municipality. The model accounts for changes in distribution of effort as recycling tonnages displace disposal tonnages, and the seven different cases examined all show that curbside collection programs that manage up to between 31% and 37% of the waste stream should result in overall system savings. These savings accrue partially because of assumed cost differences in tip fees for recyclables and disposed wastes, and also because recycling can result in a more efficient, cost-effective collection program. These results imply that increases in recycling are justifiable due to cost-savings alone, not on more difficult to measure factors that may not impact program budgets

  15. Modeling-Enabled Systems Nutritional Immunology

    Directory of Open Access Journals (Sweden)

    Meghna eVerma

    2016-02-01

    Full Text Available This review highlights the fundamental role of nutrition in the maintenance of health, the immune response and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition and the immune system interact to delineate health and disease. The review sets an unconventional path to applying complex science methodologies to nutritional immunology research, discovery and development through ‘use cases’ centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, that include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism.

  16. Model based management of a reservoir system

    Energy Technology Data Exchange (ETDEWEB)

    Scharaw, B.; Westerhoff, T. [Fraunhofer IITB, Ilmenau (Germany). Anwendungszentrum Systemtechnik; Puta, H.; Wernstedt, J. [Technische Univ. Ilmenau (Germany)

    2000-07-01

    The main goals of reservoir management systems consist of prevention against flood water damages, the catchment of raw water and keeping all of the quality parameters within their limits besides controlling the water flows. In consideration of these goals a system model of the complete reservoir system Ohra-Schmalwasser-Tambach Dietharz was developed. This model has been used to develop optimized strategies for minimization of raw water production cost, for maximization of electrical energy production and to cover flood situations, as well. Therefore a proper forecast of the inflow to the reservoir from the catchment areas (especially flooding rivers) and the biological processes in the reservoir is important. The forecast model for the inflow to the reservoir is based on the catchment area model of Lorent and Gevers. It uses area precipitation, water supply from the snow cover, evapotranspiration and soil wetness data to calculate the amount of flow in rivers. The other aim of the project is to ensure the raw water quality using quality models, as well. Then a quality driven raw water supply will be possible. (orig.)

  17. Modelling transitions in urban water systems.

    Science.gov (United States)

    Rauch, W; Urich, C; Bach, P M; Rogers, B C; de Haan, F J; Brown, R R; Mair, M; McCarthy, D T; Kleidorfer, M; Sitzenfrei, R; Deletic, A

    2017-12-01

    Long term planning of urban water infrastructure requires acknowledgement that transitions in the water system are driven by changes in the urban environment, as well as societal dynamics. Inherent to the complexity of these underlying processes is that the dynamics of a system's evolution cannot be explained by linear cause-effect relationships and cannot be predicted under narrow sets of assumptions. Planning therefore needs to consider the functional behaviour and performance of integrated flexible infrastructure systems under a wide range of future conditions. This paper presents the first step towards a new generation of integrated planning tools that take such an exploratory planning approach. The spatially explicit model, denoted DAnCE4Water, integrates urban development patterns, water infrastructure changes and the dynamics of socio-institutional changes. While the individual components of the DAnCE4Water model (i.e. modules for simulation of urban development, societal dynamics and evolution/performance of water infrastructure) have been developed elsewhere, this paper presents their integration into a single model. We explain the modelling framework of DAnCE4Water, its potential utility and its software implementation. The integrated model is validated for the case study of an urban catchment located in Melbourne, Australia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Active State Model for Autonomous Systems

    Science.gov (United States)

    Park, Han; Chien, Steve; Zak, Michail; James, Mark; Mackey, Ryan; Fisher, Forest

    2003-01-01

    The concept of the active state model (ASM) is an architecture for the development of advanced integrated fault-detection-and-isolation (FDI) systems for robotic land vehicles, pilotless aircraft, exploratory spacecraft, or other complex engineering systems that will be capable of autonomous operation. An FDI system based on the ASM concept would not only provide traditional diagnostic capabilities, but also integrate the FDI system under a unified framework and provide mechanism for sharing of information between FDI subsystems to fully assess the overall health of the system. The ASM concept begins with definitions borrowed from psychology, wherein a system is regarded as active when it possesses self-image, self-awareness, and an ability to make decisions itself, such that it is able to perform purposeful motions and other transitions with some degree of autonomy from the environment. For an engineering system, self-image would manifest itself as the ability to determine nominal values of sensor data by use of a mathematical model of itself, and selfawareness would manifest itself as the ability to relate sensor data to their nominal values. The ASM for such a system may start with the closed-loop control dynamics that describe the evolution of state variables. As soon as this model was supplemented with nominal values of sensor data, it would possess self-image. The ability to process the current sensor data and compare them with the nominal values would represent self-awareness. On the basis of self-image and self-awareness, the ASM provides the capability for self-identification, detection of abnormalities, and self-diagnosis.

  19. Size and complexity in model financial systems.

    Science.gov (United States)

    Arinaminpathy, Nimalan; Kapadia, Sujit; May, Robert M

    2012-11-06

    The global financial crisis has precipitated an increasing appreciation of the need for a systemic perspective toward financial stability. For example: What role do large banks play in systemic risk? How should capital adequacy standards recognize this role? How is stability shaped by concentration and diversification in the financial system? We explore these questions using a deliberately simplified, dynamic model of a banking system that combines three different channels for direct transmission of contagion from one bank to another: liquidity hoarding, asset price contagion, and the propagation of defaults via counterparty credit risk. Importantly, we also introduce a mechanism for capturing how swings in "confidence" in the system may contribute to instability. Our results highlight that the importance of relatively large, well-connected banks in system stability scales more than proportionately with their size: the impact of their collapse arises not only from their connectivity, but also from their effect on confidence in the system. Imposing tougher capital requirements on larger banks than smaller ones can thus enhance the resilience of the system. Moreover, these effects are more pronounced in more concentrated systems, and continue to apply, even when allowing for potential diversification benefits that may be realized by larger banks. We discuss some tentative implications for policy, as well as conceptual analogies in ecosystem stability and in the control of infectious diseases.

  20. A Modeling Pattern for Layered System Interfaces

    Science.gov (United States)

    Shames, Peter M.; Sarrel, Marc A.

    2015-01-01

    Communications between systems is often initially represented at a single, high level of abstraction, a link between components. During design evolution it is usually necessary to elaborate the interface model, defining it from several different, related viewpoints and levels of abstraction. This paper presents a pattern to model such multi-layered interface architectures simply and efficiently, in a way that supports expression of technical complexity, interfaces and behavior, and analysis of complexity. Each viewpoint and layer of abstraction has its own properties and behaviors. System elements are logically connected both horizontally along the communication path, and vertically across the different layers of protocols. The performance of upper layers depends on the performance of lower layers, yet the implementation of lower layers is intentionally opaque to upper layers. Upper layers are hidden from lower layers except as sources and sinks of data. The system elements may not be linked directly at each horizontal layer but only via a communication path, and end-to-end communications may depend on intermediate components that are hidden from them, but may need to be shown in certain views and analyzed for certain purposes. This architectural model pattern uses methods described in ISO 42010, Recommended Practice for Architectural Description of Software-intensive Systems and CCSDS 311.0-M-1, Reference Architecture for Space Data Systems (RASDS). A set of useful viewpoints and views are presented, along with the associated modeling representations, stakeholders and concerns. These viewpoints, views, and concerns then inform the modeling pattern. This pattern permits viewing the system from several different perspectives and at different layers of abstraction. An external viewpoint treats the systems of interest as black boxes and focuses on the applications view, another view exposes the details of the connections and other components between the black boxes